角膜真菌感染黏附分子机制的实验研究
摘要
目的:
通过构建真菌与角膜上皮细胞相互作用的三种模型,探讨角膜真菌感染过程中黏附的分子机制和生物学效应。
方法:
第一部分真菌激活人角膜上皮细胞FAK信号转导通路的体外实验研究
将三种常见致病真菌(白色念珠菌、烟曲霉菌和茄病镰刀菌)分别与人角膜上皮细胞共孵育,MTT法检测FAK信号通路抑制剂染料木黄酮(genistein)的对人角膜上皮细胞的细胞毒性作用;RT-PCR检测真菌黏附人角膜上皮细胞后不同时间细胞外基质层连蛋白(LN)、纤连蛋白(FN)、玻连蛋白(VN)、Ⅳ型胶原(COLIV)、跨膜蛋白整合素αV(ITGαV)、整合素β1(ITGβ1),以及FAK信号通路中FAK1、FAK2和桩蛋白(PAX)基因的表达情况;Western blot的方法检测黏附信号转导途径相关蛋白ITGβ1、FAK和PAX的表达,以及染料木黄酮对真菌刺激人角膜上皮细胞FAK信息通路活化的抑制作用;免疫细胞化学方法观察人角膜上皮细胞与真菌相互作用过程中LN、FN和FAK的表达;激光共聚焦显微镜对FN、FAK和PAX进行了细胞定位,并观察真菌刺激后人角膜上皮细胞骨架的变化;流式细胞仪定量检测人角膜上皮细胞ITGβ1与PAX在真菌黏附后表达的改变;光学显微镜观察真菌与人角膜上皮细胞黏附数量,记录并测定了黏附后积分光密度值(OD);扫描及投射电镜观察了真菌与人角膜上皮细胞黏附后,细胞超微结构的改变。
第二部分真菌对人角膜上皮细胞黏附移行能力的影响
利用Transwell小室构建真菌与人角膜上皮细胞共培养体系,建立三种常见致病真菌(白色念珠菌、烟曲霉菌和茄病镰刀菌)与人角膜上皮细胞相互作用的模型,实验共分四组,第一组:人角膜上皮细胞接种于上室内凝胶上,待80%融合后在下室加入10~8CFU(colony forming unit)/ml的真菌悬液,进行共培养;第二组:用染料木黄酮(200μM)200u1预先与细胞共培养60min后再加入上述浓度的真菌在下室;第三组:用染料木黄酮(200μM)200 u1预先与细胞共培养60min,吸去上清,用DMEM反复冲洗后,下室中加入一定体积的DMEM培养基;第四组:以未用抑制剂和真菌刺激的细胞作为空白对照,各组相互作用48h,对穿过Matrigel到达滤膜下方的人角膜上皮细胞进行HE染色,拍照记录并测定积分光密度,以评价真菌及其代谢产物对人角膜上皮细胞移行功能的影响,并进一步探讨FAK在上述过程中的作用。
第三部分黏附相关蛋白在小鼠角膜真菌感染中的表达
选用近交系BALB/c小鼠,应用角膜表层镜法,即在小鼠角膜表面覆盖大鼠角膜片,二者层间注入菌液(10~6CFU),缝合眼睑,建立三种常见致病真菌(白色念珠菌、烟曲霉菌和茄病镰刀菌)的真菌性角膜炎动物模型。染料木黄酮处理组在角膜接种菌液前60min,环绕实验眼角膜缘球结膜下注射FAK特异性抑制剂染料木黄酮(200μM)10u1,实验组注射等量0.02MPBS。裂隙灯显微镜观察接种菌液后6、12、18、24和48h角膜病变特点,拍照记录;应用HE染色进行组织病理学观察;应用免疫组织化学方法检测以上各时间点LN、ITGβ1和FAK蛋白的表达情况。
结果:
第一部分MTT法检测FAK抑制剂(染料木黄酮)终浓度200uM是对细胞毒性较小的最大抑制浓度。细胞外基质(LN、FN)、跨膜蛋白整合素ITGβ1,以及FAK信号通路中FAK和PAX基因均参与真菌与人角膜上皮细胞的黏附过程;FAK信号转导途径在人角膜上皮细胞与真菌接触后快速启动并激活下游蛋白,应用抑制剂后信号蛋白表达均不同程度减低;免疫细胞化学观察人角膜上皮细胞与真菌相互作用过程中LN、FN和FAK表达均增强,其中FAK表达呈强阳性;激光共聚焦显微镜显示FN定位于细胞外基质,FAK和PAX定位于细胞膜的内表面,并发现真菌刺激后,细胞骨架发生明显变化;流式细胞仪检测结果提示真菌与ITGβ1在瞬间迅速结合,染料木黄酮可明显抑制PAX表达;光学显微镜和积分光密度结果进一步证实了真菌黏附及染料木黄酮的抑制作用;电子显微镜观察到真菌黏附后人角膜上皮细胞出现细胞器结构紊乱、胞膜边缘波动和细胞内吞等超微结构的改变。
第二部分利用Transwell小室成功构建三种常见致病真菌与人角膜上皮细胞相互作用的模型,接种真菌及其代谢产物刺激人角膜上皮细胞48小时后,结果发现,真菌可显著增强细胞的移行能力;用FAK抑制剂染料木黄酮先与位于Transwell上室的人角膜上皮细胞作用后发现,与未受FAK抑制剂作用的人角膜上皮细胞相比,FAK抑制剂不仅能降低人角膜上皮细胞固有的移行能力,且可明显降低真菌诱导的移行能力增强作用。
第三部分裂隙灯显微镜观察接种菌液后6、12、18、24和48h,实验组和染料木黄酮处理组角膜上皮不同程度地弥漫性水肿、混浊,病变进行性加重;HE染色组织病理学观察结果提示角膜接种菌液后实验组和染料木黄酮处理组角膜上皮组织均有不同程度的水肿增厚,24h和48h组局部出现炎细胞浸润;免疫组织化学检测LN、ITGβ1和FAK均有表达,FAK的表达呈强阳性,染料木黄酮处理组FAK表达明显减低。
结论:
真菌刺激人角膜上皮细胞,通过活化细胞外基质,结合跨膜受体,激活FAK信号转导通路,可以增强角膜上皮细胞与真菌黏附能力,FAK抑制剂可有效减弱真菌诱导的人角膜上皮细胞的黏附功能。
通过真菌刺激人角膜上皮细胞FAK信号转到通路活化,可以增强角膜上皮细胞与真菌移行能力,FAK抑制剂可减弱真菌诱导的人角膜上皮细胞黏附移行等生物学行为的改变。
黏附是真菌侵入体内并发挥作用的前提,FAK信息通路的快速激活是角膜上皮细胞对真菌感染做出应答的一个早期事件。
Objective To study the molecule mechanisms of adherence and its biological effects in keratomycosis through three kinds of constructed fungus and human corneal epithelial cells interaction models.
Methods
PartⅠIn vitro study of human corneal epithelial cells' FAK signal transduction pathway activated by fungus.
The three common pathogenic fungi(Candida albicans,Aspergillus fumigatus and Fusarium solani) were co-incubated with human corneal epithelial cells respectively. MTT assay FAK signaling pathway inhibitor genistein on human corneal epithelial cell cytotoxicity;RT-PCR detection of human corneal epithelial cells adhesion to fungus at different times,extracellular matrix protein including laminin(LN),fibronectin(FN),FN glass(VN),Ⅳcollagen(COLⅣ),transmembrane protein integrinαⅤ(ITGαⅤ),integrinβ1(ITGβ1),as well as the FAK signaling pathway FAK1,FAK2 and Paxillin(PAX) gene expression;Western blot detection of the signal transduction pathway adhesion-associated protein ITGβ1,FAK and PAX expression and the inhibition of genistein. Immunocytochemical method was used to observe the LN,FN and FAK expression in human corneal epithelial cells during interaction with the fungues;Laser scanning confocal microscope had a cell positioning on FN,FAK and PAX,observed the changing of the human corneal epithelial cytoskeleton after stimulated by fungues;Quantitatived by flow cytometry to detect of human corneal epithelial cells with PAX at ITGβ1 fungal expression after adhesion;Optical microscopy quantitied the fungues and human corneal epithelial cell adhesion and recorded to determination the integral optical density(OD) afrer adhesion;Scanning and transmitted electron microscope observed the changing of cell ultrastructure after fungues and human corneal epithelial cell adhesion.
PartⅡEffects of fungnes on the capacity of adhesion and migration to human corneal epithelial cells
Fungues with human corneal epithelial cells co-culture system were constructed by Transwell chamber.After setting up the the model,three common pathogenic fungues (Candida albicans,Aspergillus fumigatus and Fusarium solani) interacted with human corneal epithelial cells in four groups.GroupⅠ:Human corneal epithelial cells on the interior gel,80%of the integration to be the next room after the add 108CFU(colony forming unit)/ml suspension of the fungus,the co-culture;GroupⅡ:With genistein (200μM) 200 u1 pre-and co-cultured cells after 60min by adding the above-mentioned fungi concentration the next room;GroupⅢ:With genistein(200μM) 200 u1 cells co-cultured with pre-60min,the supernatant go smoke with DMEM after repeated washing,the next room must add DMEM medium size;GroupⅣ:The use of inhibitors and fungi did not stimulate the cells as blank control.After Interaction in each group for 48h,HE stained the human corneal epithelial cells getting through the Matrigel membrane on the bottom.Recorded and integral optical density measured to evaluate the effects of fungus and its metabolites on human corneal epithelial cell migration function.To further explore the role of FAK in the above process.
PartⅢExpression of adhesion-related proteins in fungal corneal infections of mice.
Application of the corneal surface microscopy on inbred strain BALB/c mice cornea,thus,a full-thickness rat corneal graft was covered on the recipient bed.Three common pathogenic fungues(Candida albicans,Aspergillus fumigatus and Fusarium solani) was injected into the two layers(106CFU) and eyelid was sutured to set up three common pathogenic fungi animal models.Genistein treatment group in the cornea before vaccination bacilli 60min.Experimental cornea around the edge of subconjunctival injection of FAK inhibitor genistein(200μM) 10u1 and experimental group was injected equivalent 0.02MPBS.Slit lamp microscope observed the keratopathy features after inoculation 6,12,18,24 and 48h and camera recorded.HE staineding for histological observation and immunohistochemical methods at different time points more than LN, ITGβ1 and the expression of FAK protein.
Results
PartⅠ
MTT assay FAK inhibitor(genistein) 200uM final concentration is the greatest cytotoxicity smaller inhibitory concentration;Extracellular matrix(LN,FN),integrin transmembrane protein ITGβ1,as well as the FAK signaling pathway in both FAK and PAX genes involved in fungal and human corneal epithelial cells adhesion process;FAK signal transduction pathways in human corneal epithelial cells in contact with the fungus Quick Start and activate the downstream protein,the application of inhibitors of protein expression after the signals were reduced to varying degrees;Immunocytochemical observation of human corneal epithelial cells during interaction with the fungal LN,FN and FAK expression increased FAK expression was one of strong positive;The results of flow cytometry suggest that ITGβ1 fungues and rapidly at the moment with genistein can inhibit the expression of PAX;Optical microscope and the results of integral optical density is further evidence of fungal adhesion and inhibition of genistein;Electron microscope showed that the human corneal epithelial cells adhered to fungues and appeared disordered cell structure,cell membrane fluctuations and the edge of endocytosis in ultrastructure.
PartⅡ
Successful use of Transwell chambers to build three common pathogenic fungues and human corneal epithelial cells interaction model,inoculation of fungues and its metabolites stimulate human corneal epithelial cells for 48 hours.It was found that fungi can significantly enhance the ability of transitional cell;With FAK inhibitor genistein on with the Transwell chamber at the role of human corneal epithelial cells showed that FAK inhibitors and the role of non-corneal epithelial cells compared to people,FAK inhibitors reduce not only the inherent human corneal epithelial cells of the transitional capacity, and can significantly reduce the ability of fungal-induced enhancement of migration.
PartⅢ
Slit lamp microscope after inoculation 6,12,18,24 and 48h,the experimental group and the genistein treatment group to varying degrees of corneal epithelial diffuse edema, turbidity,increase sexual diseases;Histopathological observation of HE staining results suggest that bacteria inoculated after corneal experimental group and genistein treatment group had corneal epithelial tissue thickening of varying degrees of edema,24h and 48h group of local infiltration of inflammatory cells occur;Immunohistochemical detection of LN,ITGβ1 and FAK expression has,FAK expression was strongly positive,genistein treatment group was significantly lower expression of FAK.
Conclusion
Fungues stimulate human corneal epithelial cells through the activation of extracellular matrix,combined with transmembrane receptors,activation of FAK signal transduction pathway.It can enhance the capacity of human corneal epithelial cells adhesion to fungues.The FAK inhibitors could be effective fungal-induced weakening of human corneal epithelial cells adhesion function.
Through fungues stimulate human corneal epithelial cells to FAK signal pathway activation can enhance human corneal epithelial cells adherence and migration capacity, FAK inhibitors could be induced reduced fungues to human corneal epithelial cell adhesion,thus the biological behavior of transitional change.
Adhesion play a important role in the invasion of fungues and as a premise,the FAK signal transduction pathway activation express access information are corneal epithelial cells respond to fungal infection of an early case.
通过构建真菌与角膜上皮细胞相互作用的三种模型,探讨角膜真菌感染过程中黏附的分子机制和生物学效应。
方法:
第一部分真菌激活人角膜上皮细胞FAK信号转导通路的体外实验研究
将三种常见致病真菌(白色念珠菌、烟曲霉菌和茄病镰刀菌)分别与人角膜上皮细胞共孵育,MTT法检测FAK信号通路抑制剂染料木黄酮(genistein)的对人角膜上皮细胞的细胞毒性作用;RT-PCR检测真菌黏附人角膜上皮细胞后不同时间细胞外基质层连蛋白(LN)、纤连蛋白(FN)、玻连蛋白(VN)、Ⅳ型胶原(COLIV)、跨膜蛋白整合素αV(ITGαV)、整合素β1(ITGβ1),以及FAK信号通路中FAK1、FAK2和桩蛋白(PAX)基因的表达情况;Western blot的方法检测黏附信号转导途径相关蛋白ITGβ1、FAK和PAX的表达,以及染料木黄酮对真菌刺激人角膜上皮细胞FAK信息通路活化的抑制作用;免疫细胞化学方法观察人角膜上皮细胞与真菌相互作用过程中LN、FN和FAK的表达;激光共聚焦显微镜对FN、FAK和PAX进行了细胞定位,并观察真菌刺激后人角膜上皮细胞骨架的变化;流式细胞仪定量检测人角膜上皮细胞ITGβ1与PAX在真菌黏附后表达的改变;光学显微镜观察真菌与人角膜上皮细胞黏附数量,记录并测定了黏附后积分光密度值(OD);扫描及投射电镜观察了真菌与人角膜上皮细胞黏附后,细胞超微结构的改变。
第二部分真菌对人角膜上皮细胞黏附移行能力的影响
利用Transwell小室构建真菌与人角膜上皮细胞共培养体系,建立三种常见致病真菌(白色念珠菌、烟曲霉菌和茄病镰刀菌)与人角膜上皮细胞相互作用的模型,实验共分四组,第一组:人角膜上皮细胞接种于上室内凝胶上,待80%融合后在下室加入10~8CFU(colony forming unit)/ml的真菌悬液,进行共培养;第二组:用染料木黄酮(200μM)200u1预先与细胞共培养60min后再加入上述浓度的真菌在下室;第三组:用染料木黄酮(200μM)200 u1预先与细胞共培养60min,吸去上清,用DMEM反复冲洗后,下室中加入一定体积的DMEM培养基;第四组:以未用抑制剂和真菌刺激的细胞作为空白对照,各组相互作用48h,对穿过Matrigel到达滤膜下方的人角膜上皮细胞进行HE染色,拍照记录并测定积分光密度,以评价真菌及其代谢产物对人角膜上皮细胞移行功能的影响,并进一步探讨FAK在上述过程中的作用。
第三部分黏附相关蛋白在小鼠角膜真菌感染中的表达
选用近交系BALB/c小鼠,应用角膜表层镜法,即在小鼠角膜表面覆盖大鼠角膜片,二者层间注入菌液(10~6CFU),缝合眼睑,建立三种常见致病真菌(白色念珠菌、烟曲霉菌和茄病镰刀菌)的真菌性角膜炎动物模型。染料木黄酮处理组在角膜接种菌液前60min,环绕实验眼角膜缘球结膜下注射FAK特异性抑制剂染料木黄酮(200μM)10u1,实验组注射等量0.02MPBS。裂隙灯显微镜观察接种菌液后6、12、18、24和48h角膜病变特点,拍照记录;应用HE染色进行组织病理学观察;应用免疫组织化学方法检测以上各时间点LN、ITGβ1和FAK蛋白的表达情况。
结果:
第一部分MTT法检测FAK抑制剂(染料木黄酮)终浓度200uM是对细胞毒性较小的最大抑制浓度。细胞外基质(LN、FN)、跨膜蛋白整合素ITGβ1,以及FAK信号通路中FAK和PAX基因均参与真菌与人角膜上皮细胞的黏附过程;FAK信号转导途径在人角膜上皮细胞与真菌接触后快速启动并激活下游蛋白,应用抑制剂后信号蛋白表达均不同程度减低;免疫细胞化学观察人角膜上皮细胞与真菌相互作用过程中LN、FN和FAK表达均增强,其中FAK表达呈强阳性;激光共聚焦显微镜显示FN定位于细胞外基质,FAK和PAX定位于细胞膜的内表面,并发现真菌刺激后,细胞骨架发生明显变化;流式细胞仪检测结果提示真菌与ITGβ1在瞬间迅速结合,染料木黄酮可明显抑制PAX表达;光学显微镜和积分光密度结果进一步证实了真菌黏附及染料木黄酮的抑制作用;电子显微镜观察到真菌黏附后人角膜上皮细胞出现细胞器结构紊乱、胞膜边缘波动和细胞内吞等超微结构的改变。
第二部分利用Transwell小室成功构建三种常见致病真菌与人角膜上皮细胞相互作用的模型,接种真菌及其代谢产物刺激人角膜上皮细胞48小时后,结果发现,真菌可显著增强细胞的移行能力;用FAK抑制剂染料木黄酮先与位于Transwell上室的人角膜上皮细胞作用后发现,与未受FAK抑制剂作用的人角膜上皮细胞相比,FAK抑制剂不仅能降低人角膜上皮细胞固有的移行能力,且可明显降低真菌诱导的移行能力增强作用。
第三部分裂隙灯显微镜观察接种菌液后6、12、18、24和48h,实验组和染料木黄酮处理组角膜上皮不同程度地弥漫性水肿、混浊,病变进行性加重;HE染色组织病理学观察结果提示角膜接种菌液后实验组和染料木黄酮处理组角膜上皮组织均有不同程度的水肿增厚,24h和48h组局部出现炎细胞浸润;免疫组织化学检测LN、ITGβ1和FAK均有表达,FAK的表达呈强阳性,染料木黄酮处理组FAK表达明显减低。
结论:
真菌刺激人角膜上皮细胞,通过活化细胞外基质,结合跨膜受体,激活FAK信号转导通路,可以增强角膜上皮细胞与真菌黏附能力,FAK抑制剂可有效减弱真菌诱导的人角膜上皮细胞的黏附功能。
通过真菌刺激人角膜上皮细胞FAK信号转到通路活化,可以增强角膜上皮细胞与真菌移行能力,FAK抑制剂可减弱真菌诱导的人角膜上皮细胞黏附移行等生物学行为的改变。
黏附是真菌侵入体内并发挥作用的前提,FAK信息通路的快速激活是角膜上皮细胞对真菌感染做出应答的一个早期事件。
Objective To study the molecule mechanisms of adherence and its biological effects in keratomycosis through three kinds of constructed fungus and human corneal epithelial cells interaction models.
Methods
PartⅠIn vitro study of human corneal epithelial cells' FAK signal transduction pathway activated by fungus.
The three common pathogenic fungi(Candida albicans,Aspergillus fumigatus and Fusarium solani) were co-incubated with human corneal epithelial cells respectively. MTT assay FAK signaling pathway inhibitor genistein on human corneal epithelial cell cytotoxicity;RT-PCR detection of human corneal epithelial cells adhesion to fungus at different times,extracellular matrix protein including laminin(LN),fibronectin(FN),FN glass(VN),Ⅳcollagen(COLⅣ),transmembrane protein integrinαⅤ(ITGαⅤ),integrinβ1(ITGβ1),as well as the FAK signaling pathway FAK1,FAK2 and Paxillin(PAX) gene expression;Western blot detection of the signal transduction pathway adhesion-associated protein ITGβ1,FAK and PAX expression and the inhibition of genistein. Immunocytochemical method was used to observe the LN,FN and FAK expression in human corneal epithelial cells during interaction with the fungues;Laser scanning confocal microscope had a cell positioning on FN,FAK and PAX,observed the changing of the human corneal epithelial cytoskeleton after stimulated by fungues;Quantitatived by flow cytometry to detect of human corneal epithelial cells with PAX at ITGβ1 fungal expression after adhesion;Optical microscopy quantitied the fungues and human corneal epithelial cell adhesion and recorded to determination the integral optical density(OD) afrer adhesion;Scanning and transmitted electron microscope observed the changing of cell ultrastructure after fungues and human corneal epithelial cell adhesion.
PartⅡEffects of fungnes on the capacity of adhesion and migration to human corneal epithelial cells
Fungues with human corneal epithelial cells co-culture system were constructed by Transwell chamber.After setting up the the model,three common pathogenic fungues (Candida albicans,Aspergillus fumigatus and Fusarium solani) interacted with human corneal epithelial cells in four groups.GroupⅠ:Human corneal epithelial cells on the interior gel,80%of the integration to be the next room after the add 108CFU(colony forming unit)/ml suspension of the fungus,the co-culture;GroupⅡ:With genistein (200μM) 200 u1 pre-and co-cultured cells after 60min by adding the above-mentioned fungi concentration the next room;GroupⅢ:With genistein(200μM) 200 u1 cells co-cultured with pre-60min,the supernatant go smoke with DMEM after repeated washing,the next room must add DMEM medium size;GroupⅣ:The use of inhibitors and fungi did not stimulate the cells as blank control.After Interaction in each group for 48h,HE stained the human corneal epithelial cells getting through the Matrigel membrane on the bottom.Recorded and integral optical density measured to evaluate the effects of fungus and its metabolites on human corneal epithelial cell migration function.To further explore the role of FAK in the above process.
PartⅢExpression of adhesion-related proteins in fungal corneal infections of mice.
Application of the corneal surface microscopy on inbred strain BALB/c mice cornea,thus,a full-thickness rat corneal graft was covered on the recipient bed.Three common pathogenic fungues(Candida albicans,Aspergillus fumigatus and Fusarium solani) was injected into the two layers(106CFU) and eyelid was sutured to set up three common pathogenic fungi animal models.Genistein treatment group in the cornea before vaccination bacilli 60min.Experimental cornea around the edge of subconjunctival injection of FAK inhibitor genistein(200μM) 10u1 and experimental group was injected equivalent 0.02MPBS.Slit lamp microscope observed the keratopathy features after inoculation 6,12,18,24 and 48h and camera recorded.HE staineding for histological observation and immunohistochemical methods at different time points more than LN, ITGβ1 and the expression of FAK protein.
Results
PartⅠ
MTT assay FAK inhibitor(genistein) 200uM final concentration is the greatest cytotoxicity smaller inhibitory concentration;Extracellular matrix(LN,FN),integrin transmembrane protein ITGβ1,as well as the FAK signaling pathway in both FAK and PAX genes involved in fungal and human corneal epithelial cells adhesion process;FAK signal transduction pathways in human corneal epithelial cells in contact with the fungus Quick Start and activate the downstream protein,the application of inhibitors of protein expression after the signals were reduced to varying degrees;Immunocytochemical observation of human corneal epithelial cells during interaction with the fungal LN,FN and FAK expression increased FAK expression was one of strong positive;The results of flow cytometry suggest that ITGβ1 fungues and rapidly at the moment with genistein can inhibit the expression of PAX;Optical microscope and the results of integral optical density is further evidence of fungal adhesion and inhibition of genistein;Electron microscope showed that the human corneal epithelial cells adhered to fungues and appeared disordered cell structure,cell membrane fluctuations and the edge of endocytosis in ultrastructure.
PartⅡ
Successful use of Transwell chambers to build three common pathogenic fungues and human corneal epithelial cells interaction model,inoculation of fungues and its metabolites stimulate human corneal epithelial cells for 48 hours.It was found that fungi can significantly enhance the ability of transitional cell;With FAK inhibitor genistein on with the Transwell chamber at the role of human corneal epithelial cells showed that FAK inhibitors and the role of non-corneal epithelial cells compared to people,FAK inhibitors reduce not only the inherent human corneal epithelial cells of the transitional capacity, and can significantly reduce the ability of fungal-induced enhancement of migration.
PartⅢ
Slit lamp microscope after inoculation 6,12,18,24 and 48h,the experimental group and the genistein treatment group to varying degrees of corneal epithelial diffuse edema, turbidity,increase sexual diseases;Histopathological observation of HE staining results suggest that bacteria inoculated after corneal experimental group and genistein treatment group had corneal epithelial tissue thickening of varying degrees of edema,24h and 48h group of local infiltration of inflammatory cells occur;Immunohistochemical detection of LN,ITGβ1 and FAK expression has,FAK expression was strongly positive,genistein treatment group was significantly lower expression of FAK.
Conclusion
Fungues stimulate human corneal epithelial cells through the activation of extracellular matrix,combined with transmembrane receptors,activation of FAK signal transduction pathway.It can enhance the capacity of human corneal epithelial cells adhesion to fungues.The FAK inhibitors could be effective fungal-induced weakening of human corneal epithelial cells adhesion function.
Through fungues stimulate human corneal epithelial cells to FAK signal pathway activation can enhance human corneal epithelial cells adherence and migration capacity, FAK inhibitors could be induced reduced fungues to human corneal epithelial cell adhesion,thus the biological behavior of transitional change.
Adhesion play a important role in the invasion of fungues and as a premise,the FAK signal transduction pathway activation express access information are corneal epithelial cells respond to fungal infection of an early case.
引文
1.Srinivasan M,Gonzales CA,George C,et al.Epidemiology and aetiological diagnosis of corneal ulceration in Madurai,south India.Br J Ophthalmol 1997,81:965-971.
2.Xie L,Dong X,Shi W.Treatment of fungal keratitis by penetrating keratoplasty.Br J Ophthalmol 2001,85:1070-1074.
3.Xie L,Shi W,Liu Z,et al.Lamellar keratoplasty for the treatment of fungal keratitis.Cornea 2002,21:33-37.
4.Sun,X.G.,Y.Zhang,R.Li,et al.Etiological analysis on ocular fungal infection in the period of 1989-2000.Chin Med J(Engl) 2004,117:598.
5.张文华,潘志强,王智群,等.化脓性角膜溃疡常见致病菌的变迁.中华眼科杂志2002,38:8-12.
6.Tanure MAG,Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea 2000;19:307-312.
7.YanSZ,RodriguesRG,Cahn-HidalgoD,etal.Hemoglobin induces binding of several extracellular matrix proteins to Candida albicans.J Biol Chem,1998,273:5638-5644.
8.Monteiro da Silva JL,Andreotti PF,Benard G,etal.Epithelial cells treated with genistein inhibit adhesion and endocytosis of Paracoccidioides brasiliensis.Antonie Van Leeuwenhoek,2007,92(1):129-135.
9.Dong X,Shi W,Zeng Q,et al.Roles of adherence and matrix metalloprotei- nases in growth patterns of fungal pathogens in cornea.Curr Eye Res.2005 30(8):613-620.
10.Zhong B,Jiang K,Gilvary DL.Human neutrophils utilize a Rac/Cdc42-dependent MAPK pathway to direct intracellular granule mobilization toward ingested microbial pathogens.Blood,2003,101:3240-3248.
11.Whitcher JP,Srinivasan M,Upadhyay MP.Corneal blindness:a global perspective.Bull World Health Organ,2001,79:214-221.
12.Xie L,Dong X,Shi W.Treatment of fungal keratitis by penetrating keratoplasty.Br J Ophthalrnol,2001,85:1070-1074.
13.Gopinathan U,Garg P,Fernandes M,et al.The epidemiological features and laboratory results of fungal keratitis:a 10-year review at a referral eye care centre in South India.Cornea,2002,21:555-559.
14.Chowdhary A,Singh K.Spectrum of Fungal Keratitis in North India.Cornea,2005,24:8-15.
15.Leck AK,Thomas PA,Hagan M,'et al.Aetiology of suppurative corneal ulcers in Ghana and South India,and epidemiology of fungal keratitis.Br J Ophthalmol,2002,86:1211-1215.
16.Upadhyay MP,Karmacharya PC,Koirala S,et al.Epidemiologic characteristics,predisposing factors,and etiologic diagnosis of corneal ulceration in Nepal.Am J Ophthalmol,1991,15:92-99.
17.Gozalbo D,Gil-Navarro I,Azorin I,et al.The cell wall-associated glyceraldehydes-3-phosphate dehydrogenase,of Candida albicans is also a fibronectin and laminin binding protein.Infect Immun,1998,66:2052-2059.
18.Hands SK,Calalb MB,Harper MC,et al.Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin.Proc Natl Acad Sci USA,1992,89(18):8487-8491.
19.Schaller MD,Borgman CA,Cobb BS,et al.pp125 FAK a structurally distinctive protein-tyrosine Icinase associated with focal adhesions.Proc Natl Acad Sci USA,1992,89(11):5192-5196.
20.Schaller MD,Parsons JT.Focal adhesion kinase:an integrin-linked protein tyrosine kinase.Trends Cell Biol,1993,3(8):258-262.
21.Ilic D,Furuta Y,Kanazawa S,et al.Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK deficient mice.Nature,1995,377(6549):539-544.
22.Hecker TP,Gladson CL.Focal adhesion kinase in cancer.Front Biosci,2003,8:S705-S714.
23.Fordin M,Gammeltoft S.Role and regulation of 90 kDa ribosomal S6 kinase(RSK) in signal transduction.Mol Cell Endocrinol,1999,151:65-77.
24.Gonzalez FA,Seth A,Raden DL,et al.Serum-induced translocation of mitogen-activated protein kinase to the cell surface ruffling membrane and the nucleus.J Cell Biol,1993,122:1089-1101.
25.Chen RH,Sarnecki C,Blenis J.Nuclear localization and regulation of the erk- and rsk-encoded protein kinases.Mol Cell Biol,1992,12:915-927.
26.Seger R,Krebs EG.Protein kinases:The Mapk signaling cascade.FASEB J,1995,9,726-735.
27.Sieg DJ,Hauck CR,Ilic D,et al.FAK integrates growth-factor and integrin signals to promote cell migration.Nat Cell Biol,2000,2(5):249-256.
28.Schlaepfer DD,Mitra SK,Ilic D.Control of motile and invasive cell phenoty by focal adhesion kinase.Biochim Biophys Acta,2004,1692(2-3):77-102.
29.Schaller MD.Biochemical signals and biological responses elicited by the focal adhesion kinase.Biochim Biophys Acta,2001,1540(1):1-21.
30.Bin Zhong.Human neutrophils utilize a Rac/Cdc42-dependent MAPK pathway to direct intracellular granule mobilization toward ingested microbial pathogens.Blood,2003,101(8):3240-3248
31.Ningfeng Tang.Inhibition of monocytic interleukin-12 production by candida albicans via selective activation of ERK mitogen-activated protein kinase.Infection and Immunity,2004,72(5):2513-2520
32.Zhong B,Jiang K,Gilvary DL,et al.Human neutrophils utilize a Rac/Cdc42-dependent MAPK pathway to direct intracellular granule mobilization toward ingested microbial pathogens.Blood,2003 101:3240-3248.
33.Sandovsky-Losica H,Segal E.Infection of HEp2 epithelial cells with Candida albicans: adherence and postadherence events.FEMS Immunol Med Microbiol,2006,46(3):470-475
34.Ibrahim-Granet O,Philippe B,Boleti H,et al.Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages.Infect Immun,2003,71(2):891-903
35.Tsarfaty I,Sandovsky-Losica H,Mittelman L,et al.Cellular actin is affected by interaction with Candida albicans.FEMS Microbiol Lett,2000,189(2):225-232
36.Park H,Myers CL,Sheppard DC,et al.Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis.Cell Microbiol,2005,7:499-510
37.Sandovsky-Losica H,Segal E.Infection of HEp2 epithelial cells with Candida albicans:adherence and postadherence events.FEMS Immunol Med Mierobiol,2006,46(3):470-475
38.Kruppa M,Calderone R.Two-component signal transduction in human fungal pathogens.FEMS Yeast Res,2006,6(2):149-159
39.Sandovsky-Losiea H,Berdicevsky I,Tsarfaty I,et al.Effect of Candida albieans metabolites)on cellular actin.FEMS Microbiol Lett,2002;24;215(1):57-62.
40.Tsarfaty I,Sandovsky-Losica H,Mittelman L,et al.Cellular actin is affected by interaction with Candida albicans.FEMS Microbiol Lett 2000,15;189(2):225-232.
41.Ridley AJ,Schwartz,MA,Burridge K,et al.Cell migration:integrating signals from front to bck.Science,2003,302(5651):1704-1709.
42.Degryse B,Orlando S,Resnati M,et al.Urokinase/urokinase receptor and vitronectin/alpha(v)beta(3) integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways.Oncogene,2001,20(16):2032-2043.
43.Cuevas BD,Abell AN,Witowsky JA,et al.MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts.EMBO J,2003,22(13):3346-3355.
44.Jo M,Thomas KS,Somlyo AV,et al.Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migration.J Biol Chem,2002,277:12479-12485.
45.Webb D J,Nguyen DHD,Gonias SL.Extracellular signal regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and Matrigel invasion.J.Cell Sci,2000,113:123-134.
46.Ridley AJ,Schwartz MA,Burridge K,et al.Cell migration:integrating signals from front to back.Science,2003,3020,1704-1709.
47.Potten CS.Cell replacement in epidermis(keratopoiesis) via discrete units of proliferation.Int Rev Cytol.1981,69:271-318.
48.Tao H,Shimizu M,Kusumoto R,et al.A dual role of FGF10 in proliferation and coordinated migration of epithelial leading edge cells during mouse eyelid development.Development.2005,132(14):3217-3230.
49.Green,Gaudry CA.Are desmosomes more than tethers for intermediate filaments? Nat Rev Mol Cell Biol.2000,1(3):208-216.
50.Usui ML,Underwood RA,Mansbridge JN,et al.Morphological evidence for the role of suprabasal keratinocytes in wound reepithelialization.Wound Repair Regen.2005,13(5):468-479.
51.Radeke HH,Ludwig RJ,Boehncke WH.Experimental approaches to lymphocyte migration in dermatology in vitro and in vivo.Exp Dermatol.2005,14(9):641-666.
52.Gonlugur U,Efeoglu T.Vascular adhesion and transendothelial migration of eosinophil leukoeytes.Cell Tissue Res.2004,318(3):473-482.
53.Sheikine YA,Hansson GK.Chemokines as potential therapeutic targets in atherosderosis.Curr Drug Targets.2006,7(1):13-27.
54.Touyz RM.Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension:role of angiotensin Ⅱ.Exp Physiol.2005,90(4):449-455.
55.von Wichert G,Sheetz MP.Mechanisms of disease:the biophysical interpretation of the ECM affects physiological and pathophysiological cellular behavior.Z Gastroenterol.2005,43(12):1329-1336.
56.Karasarides M,Chiloeches A,Havward R,et al.B-RAF is a therapeutic target in melanoma.Oncogene 2004;23:6292-6298.
57.Itoh RE,Kurokawa K,Ohba Y,et al.Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells.Mol Cell Biol.2002,22(18):6582-6591.
58.Li Z,Hannigan M,Mo Z,et al.Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42.Cell.2003,114(2):215-227.
59.Merlot S,Firtel RA.Leading the way:.Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways.J Cell Sci.2003,116(Pt 17):3471-3478.
60.Katoh H,Negishi M.RhoG activates Racl by direct interaction with the Dockl80-binding protein Elmo.Nature.2003,424(6947):461-464.
61.Cory GO,Ridley AJ.Cell motility:brakingWAVEs.Nature.2002,418(6899):732-733.
62.Snapper SB,Takeshima F,Anton I,et al.N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.Nat Cell Biol.2001,3(10):897-904.
63.Webb DJ,Parsons JT,Horwitz AF.Adhesion assembly,disassembly and turnover in migrating cells-over and over and over again.Nat Cell Biol.2002,4(4):E97-100.
64.Turner CE,West KA,Brown MC.Paxillin-ARF GAP signaling and the cytoskeleton.Curr Opin Cell Biol.2001,13(5):593-599.
65.Brahmbhatt AA,Klemke RL.ERK and RhoA differentially regulate pseudopodia growth and retraction during chemotaxis.J Biol Chem.2003,278(15):13016-13025.
66.Lee J,Ishihara A,Oxford G,et al.Regulation of cell movement is mediated by stretch-activated calcium channels.Nature.1999,400(6742):382-386.
67.Webb DJ,Nguyen D,Gonias SL.Extracellular signal regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and Matrigel invasion.J Cell Sci,2000,113,123-134.
68.Klemke RL,Cai S,Criannini AL,et al.Regulation of cell motility by mitogen-activated protein kinase.J Cell Biol,1997,137,481-492.
69.Anand-Apte B,Zetter BR,Viswanathan A,et al.Platelet-derived growth factor and fibronectin-stimulated migration are differentially regulated by the Rac and extracellular signal-regulated kinase pathways.J Biol Chem,1997,272,30688- 30692.
70.Lai CF,Chaudhary L,Fausto A,et al.Erk is essential for growth,differentiation,integrin expression,and cell function in human osteoblastic cells.J Biol Chem,2001,276,14443-14450.
71.Cho SY,Klemke RL.Extracellular-regulated kinase activation and CAS/Crk coupling regulate cell migration and suppress apoptosis during invasion of the extracellular matrix.J Cell Biol,2000,149,223- 236.
72.Cheresh DA,Leng J,Klemke RL.Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells.J Cell Biol,1999,146,1107-1116.
73.Shono T,Kanetake H,Kanda S.The role of mitogen-activated protein kinase activation within focal adhesions in chemotaxis toward FGF- 2 by murine brain capillary endothelial cells.Exp Cell Res,2001,264,275-283.
74.Xie H,Pallero MA,Gupta K,et al.EGF receptor regulation of cell motility:EGF induces disassembly of focal adhesions independently of the motility-associated PLC gamma signaling pathway.J Cell Sci,1998,111,615-624.
75.Guan JL.Role of focal adhesion kinase in integrin signaling.Int J Biochem Cell Biol,1997,29:1085-1096.
76.Hanks SK,Polte TR.Signaling through focal adhesion kinase.Bioessays,1997,19:137-145.
77.Ilic D,Damsky CH,Yamamoto T.Focal adhesion kinase:at the crossroads of signal transduction.J Cell Sci,1997,110:401-407.
78.Schlaepfer DD,Hanck CR,Sieg DJ.Signaling through focal adhesion kinase.Prog Biophys Mol Biol,1999,71:435-478.
79.Zachary I.Focal adhesion kinase.Int J Biochem Cell Biol,1997,29:929-934.
80.王丽娅,张月琴,王印其,等.中国三地区真菌性角膜病致病菌种的调查.中华眼科杂志,2000.36:138-139.
81.谢立信,史伟云,董晓光,等.108例真菌性角膜炎的临床和组织病理学研究.眼科研究,1999.17:283-285.
82.谢立信,李绍伟,史伟云,等.共焦显微镜在真菌性角膜炎临床诊断中的应用.中华眼科杂志,1999,35:7-9.
83.陈瑞娥,戴文丽,孙志坚.真菌性角膜溃疡病原菌及其诱因分析.中华检验医学杂志,2002,25:364
84.Braedel S,Radsak M,Einsele H,et al.Aspergillus fumigatus antigens activate innate immune cells via toll-like receptors 2 and 4.Br J Haematol,2004,125:392-399.
85.Meier A,Kirschning,C.J,Nikolaus T,et al.Toll-like receptor(TLR) 2 and TLR4 are essential for Aspergillus-induoed activation of marine macrophages.Cell Microbiol,2003,5:561-570.
86.Netea MG,Van Der Graaf CA,Vonk AG,et al.The role of toll-like receptor(TLR) 2 and TLR4in the host defense against disseminated candidiasis.J Infect Dis,2002,185:1483-1489.
87.Marnbula SS,Sau K,Henneke P,et al.Toll-like Receptor(TLR) Signaling in Response to Aspergillus fumigatus.J Biol Chem,2002,277:39320-39326.
88.Shoham S,Huang C,Chen JM,et al.Toll-like receptor 4 mediates intracellular signaling without TNF-alpha release in response to Cryptococcus neoformans polysaccharide capsule,J Immunol,2001,166:4620-4626.
89.Villamon E,Gozalbo D,Roig P,et al.Toll-like receptor-2 is essential in marine defenses against Candida albicans infections.Microbes Infect,2004,6:1-7.
90.Sheppard DC,Yeaman MR,Welch WH,et al.Functional and structural diversity in the Als protein family of Candida albicans.J Biol Chem,2004,279(29):30480-30489.
91.Klotz SA,Gaur NK,Lake DF,et al.Degenerate peptide recognition by Candida albieans adhesins Als5p and Als lp.Infect Immun,2004,72(4):2029-2034.
92.Gozalbo D,Gil-Navarro I,Azorin I,et al.The cell wall-associated glyeeraldehydes-3-phosphate dehydrogenase of Candida albicans is also a fibronectin and laminin binding protein.Infect Immun,1998,66:2052-2059.
93.Latge JP.Aspergillus fumigatus and aspergillosis.Clin Mierobiol Rev,1999,12:310-350.
94.Stringaro A,Crateri P,Pellegrini G,et al.Ultrastructural localization of the secretory aspartyl proteinase in Candida albicans cell wall in vitro and in experimentally infected rat vagina.Mycopathologia,1997,137:95-105.
95.Huang G,Zhang M,Erdman SE.Posttranslational modifications required for cell surface localization and function of the fungal adhesin Agalp.Eukaryot Cell,2003,2(5):1099-1114.
96.Calderone R,Suzuki S,Cannon R,et al.Candida albicans:adherence,signaling and virulence.Med Mycol,2000,38 Suppl 1:125-137.
97.Tronchin G,Esnault K,Sanchez M,et al.Purification and partial characterization of a 32-kilodalton sialic acid-specific lectin from Aspergillus fumigatus.Infect immun,2002,70(12):6891-6895.
98.Latg(?) JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev,1999,12(2):310-350.
99.Penalver MC,O' Connor JE,Martinez JP,et al.Binding of human fibronectin to Aspergillus fumigatus conidia[J].Infect Immun,1996,64(4):1146-1153..
100.Kumar CPG,Menon T.Biofilm production by clinical isolate of Candida species.Medical Mycology,2006,44(1):99-10.
101.Al-Fattani MA,Douglas LJ.Penetration of Candida biofilms by antifungal agents.Antimicrob Agents Chemother,2004,48(9):3291-3297.
102.Mitchell BM,Wu TG,Chong EM,et al.Expression of matrix metalloproteinases 2 and 9 in experimental corneal injury and fungal keratitis.Cornea,2007,26(5):589-593.
103.Rohini G,Murugeswari P,Prajna NV,et al.Matrix metalloproteinases(MMP-8,MMP-9) and the tissue inhibitors of metalloproteinases(TIMP-1,TIMP-2) in patients with fungal keratitis.Cornea,2007,26(2):207-211.
104.Monteiro da Silva JL,Andreotti PF,Benard G,et al.Epithelial cells treated with genistein inhibit adhesion and endoeytosis of Paracoccidioides brasiliensis.Antonie Van Leeuwenhoek,2007,92(1):129-135.
105.Jackson BE,Wilhelmus KR,Mitchell BM.Genetically regulated filamentation contributes to Candida albicans virulence during corneal infection.Microb Pathog,2007,42(2-3):88-93.
106.Leidich SD,Ibrahim AS,Fu Y,et al.Cloning and disruption of caPLB1,a phospholipase B gene involved in the pathogenicity ofCandida albicans.J Biol Chem,1998,273:26078-26086.
1.Srinivasan M,Gonzales CA,George C,et al.Epidemiology and aetiological diagnosis of corneal ulceration in Madurai,south India.Br J Ophthalmol 1997,81:965-971
2.Xie L,Dong X,Shi W.Treatment of fungal keratitis by penetrating keratoplasty.Br J Ophthalmol 2001,85:1070-1074
3.Xie L,Shi W,Liu Z,et al.Lamellar keratoplasty for the treatment of fungal keratitis.Cornea 2002,21:33-37
4.Sun,X.G.,Y.Zhang,R.Li,et al.Etiological analysis on ocular fungal infection in the period of 1989-2000.Chin Med J(Engl) 2004,117:598
5.张文华,潘志强,王智群,等.化脓性角膜溃疡常见致病菌的变迁.中华眼科杂志2002,38:8-12
6.Tanure MAG.Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea 2000;19:307-312
7.Chowdhary A,Singh K.Spectrum of Fungal Keratitis in North India.Cornea,2005,24:8-15
8.Rauceo JM,De Armond R,Otoo H,et al.Threonine-rich repeats increase fibronectin binding in the Candida albieans adhesin Als5p.Eukaryot Cell,2006,5(10):1664-1673
9.YanSZ,RodriguesRG.Cahn-HidalgoD,etal.Hemoglobin induces binding of several extracellular matrix proteins to Candida albicans.J Biol Chem,1998,273:5638-5644
10.Monteiro da Silva JL,Andreotti PF,Benard G,etal.Epithelial cells treated with genistein inhibit adhesion and endocytosis of Paracoccidioides brasiliensis.Antonie Van Leeuwenhoek,2007,92(1):129-135
11.HoyerLL,HechtJE.The ALS6 and ALS7 genes of Candida albicans,Yeast,2000,16:847-855
12,FuY,RiegG,Fonzi WA,etal.Expression of the Candida albicans gene ALS1 in Saccharomycescerevisiae induces adherence to endothelial and epithelialcells.InfectImmun,1998,66:1783-1786
13.LozaL,Fu Y,Ibrahim AS,etal.Functional analysis of theCandida albicans ALS1 gene product.Yeast,2004,21:473-482
14.Nobile CJ,Andes DR,Nett JE,et al.Critical role of Bcrl-dependent adhesins in C.albicans biofilm formation in vitro and in vivo.PLoS Pathog,2006,2(7):e63
15.Gaur NK and Klotz SA.Expression,cloning,and characterization of a Candida albicans gene,ALA1,that confers adherence properties upon Saccharomyces cerevisiae for extra cellular matrix proteins.Infect Immun,1997,65(12):5289-5294
16.Gaur NK,Smith RL,Klotz SA.Candida albicans and Saccharomyces cerevisiae expressing ALA1/ALS5 adhere to accessible threonine,serine,or alaninepatches.CellCommun Adhes,2002,9(1):45-57
17.Park H,Myers CL,Sheppard DC,et al.Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis.Cell Microbiol,2005,7:499-510
18.Barki M,Koltin Y,van Wetter M,etal.A Candida albicans surface antigen mediating adhesion and autoaggregation in Saccharomyces cerevisiae.Infect Immun,1994,62(10):4107-4111
19.Staab JF,Sundstrom P.Genetic organization and sequence an alysis of the hypha specific cell wall protein gene HWP 1 of Candida albicans.Yeast,1998,14(7):681- 686
20.Staab JF,Bradway SD,Fidel PL,etal.Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwpl.Science,1999,283(5407):1535-1538
21.Sandini S,La Valle R,De Bernardis F,etal.The 65 kDa mannoprotein gene of Candida albicans encodes a putative beta-glucanase adhesin required for hyphal morphogenesis and experimental pathogenicity,2007,9(5):1223-38
22.Li F,Palecek SP.EAP1,a Candida albicans gene involved in binding human epithelial cells.Eukaryot Cell,2003,2(6):1266-1273
23.Iqraqui I,Carcia-sanchez S,Aubert S,et al The Yaklp ki-nase controls expression of adhesion and biofilm formation inCandida glabrata in 2Sir4p dependentpathway.MolMierobio,12005,55(4):1259-1271
24.Ghannoum MA.Potential role of phospholipase in virulence and fungal pathogenesis.Clin Microbiol Rev,2000,13:122-143
25.Leidich SD,Ibrahim AS,Fu Y,et al.Cloning and disruption of caPLB1,a phospholipase B gene involved in the pathogenicity ofCandida albieans.J Biol Chem,1998,273:26078-26086
26.Iadarola P,Lungarella G,Martorana PA,et al.Lung injury and degradation of extracellular matrix components by Aspergillns fumigatus serine proteinase.Exp Lung Res,1998,24:233-251
27.Tronchin G,Bouchara JP,Larcher G,et al.Interaction between Aspergillus fumigatus and basement membrane laminin:binding and substrate degradation.Biol Cell,1993,77:201-208
28.Iadarola P,Lungarella G,Martorana PA,et al.Lung injury and degradation of extracellular matrix components by Aspergillus fumigatus serine proteinase.Exp Lung Res,1998,24(3):233-251.
29.Dong X,Shi W,Zeng Q,et al.Roles of adherence and matrix metalloprotei- nases in growth patterns of fungal pathogens in cornea.Curt Eye Res.2005 30(8):613-620
30.Yang Q,Su QP,Wang GY,et al.Production of hybrid phage displaying secreted aspartyl proteinase epitope of Candida albicans and its application for the diagnosis of disseminated candidiasis.Mycoses.2007,50(3):165-171
31.Kaur R,Ma B,Cormack BP.A family ofglyeosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata.Proc Natl Acad Sci U S A.2007,104(18):7628-7633
32.Latge JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev,1999,12:310-350
33.Lee JD,Kolattukudy PE.Molecular cloning of the cDNA and gene for an lastinolytic aspartic proteinase from Aspergillus fumigatus and evidence of its secretion by the fungus during invasion of the host lung.Infect Immun,1995,63:3796-3803
34.Tronchin G.Esnault K,Sanchez M,et al.Purification and partial characterization of a 32-kilodalton sialic acid-specific lectin from Aspergillus fumigatus.Infect Immun,2002,70(12):6891-6895
35.Gozalbo D,Gil-Navarro I,Azorin I,et al.The cell wall-associated glyceraldehydes -3-phosphate dehydrogenase of Candida albicans is also a fibronectin and laminin binding protein.Infect Immun,1998,66:2052-2059
36.San-blas G,Travassos LR,Fries BC,et al.Fungal morphogenesis and virulence.Med Myeol,2000,38(Suppl Ⅰ ):79-86
37.Penalver MC,O'Connor JE,Martinez JP,et al.Binding of human fibronectin to Aspergillus fumigatus eonidia[J].Infect Immun,1996,64(4):1146-1153
38.Latg(?) JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev,1999,12(2):310-350
39.Kwan AH,Winefield RD,Sunde M,et al.Structural basis for rodlet assembly in fungal hydrophobins,2006,103(10):3621-3626.
40.Kriznik A,Bouillot M,Coulon J,et al.Morphological specificity of yeast and filamentous Candida albicans forms on surface properties.C R Biol,2005,328(10-11):928-935.
41.Kumar CPG,Menon T.Biofilm production by clinical isolate of Candida species.Medical Mycology,2006,44(1):99-10
42.Kumamoto CA,Vinces MD.Altemative Candida albicans lifesyle:growth on surfaces.Annu Rev Microbial,2005,59:113-133
43.Naglik JR,Challacomber SJ,Hube B.Candida albicans secreted aspartyl proteinases in vim lence and pathogenesis.Microbiol Mol Biol Rev,2003,67(3):400-428
44.Al-Fattani MA,Douglas LJ.Penctration of Candida biofilms by antifungal agents.Antimicrob Agents Chemother,2004,48(9):3291-3297
45.Kukreja N,Arora N,Singh BP,et al.Role of Glycoproteins Isolated from Epicoccum purpurascens in Host-Pathogen Interaction.Patho- biology,2007,74(3):186-192
46.Wang EW,Jung JY,Pashia ME,et al.Otopathogenic Pseudomonas aeruginosa strains as competent biofilm formers.Arch Otolaryng- ol Head Neck Surg,2005,131(11):983-989
47.Rauceo JM,De Armond R,Otoo H,et al.Thrconine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p.Eukaryot Cell,2006,500):1664-1673
48.Rauceo JM,Gaur NK,Lee KG,et al.Global cell surface conformational shift mediated by a Candida albicans adhesin.Infect Immun,2004,72(9):4948-4955
49.Sheppard DC,Yeaman MR,Welch WH,et al.Functional and structural diversity in the Als protein family of Candida albicans.J Biol Chem,2004,279(29):30480-30489
50.Klotz SA,Gaur NK,Lake DF,et al.Degenerate peptide recognition by Candida albicans adhesins Als5p and Als1p.Infect Immun,2004,72(4):2029-2034
51.Sohn K,Seny(u|¨)rek I,Fertey J,et al.An in vitro assay to study the transcriptional response during adherence of Candida albicans to different human epithelia.FEMS Yeast Res,2006,6(7):1085-1093
52.Nobile CJ,Nett JE,Andes DR,et al.Function of Candida albicans adhesin Hwpl in biofilm formation.Eukaryot Cell,2006,5(10):1604-1610
53.Gaur NK,Klotz SA.Accessibility of the peptide backbone of protein ligands is a key specificity determinant in Candida albicans SRS adherence.Microbiology,2004,150(Pt 2):277-284
54.Lee JD,Kolattukudy PE.Molecular cloning of the cDNA and gene for an elastinolytic aspartic proteinase from Aspergillus fumigatus and evidence of its secretion by the fungus during invasion of the host lung.Infect Immun,1995,63(10):3796-3803
55.Ray TL,Payne CD.Scanning electron microscopy of epidermal adherence and cavitation in murine candidiasis:A role for Candida acid proteinase.Infect Immtm,1988,56:1942-1949
56.Stringaro A,Crateri P,Pellegrini G,et al.Ultrastructural localization of the secretory aspartyl proteinase in Candida albicans cell wall in vitro and in experimentally infected rat vagina.Mycopathologia,1997,137:95-105
57.Schaller M,Korting HC,Schafer W,et al.Secreted aspartic proteinase(Sap) activity contributes to tissue damage in a model of human oral candidosis.Mol Microbiol,1999,34:169-180
58.Schaller M,Bein M,Korting HC,et al.The secreted aspartyl proteinases Sap1 and Sap2cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium.Infect Immun,2003,71:3227-3234
59.De Bernardis F,Arancia S,Morelli L,et al.Evidence that members of the secretory aspartyl proteinase gene family,in particular SAP2,are virulence factors for Candida vaginitis.J Infect Dis,1999,179:201-208
60.Andrian E,Grenier D,Rouabhia M.In vitro models of tissue penetration and destruction by Porphyromonas gingivalis.Infect Immun,2004,72:4689-4698
61.Tsai PJ,Kuo CF,Lin KY,et al.Effect of group A streptococcal cysteine protease on invasion of epithelial cells.Infect Immun,1998,66:1460-1466
62.Huang G,Zhang M,Erdman SE.Posttranslational modifications required for cell surface localization and function of the fungal adhesin Agalp.Eukaryot Cell,2003,2(5):1099-1114
63.Calderone R,Suzuki S,Cannon R,et al.Candida albieans:adherence,signaling and virulence.Med Mycol,2000,38 Suppl 1:125-137
64.Gonz(?)lez A,G(?)mez BL,Diez S,et al.Purification and partial characterization of a Paracoccidioides brasiliensis protein with capacity to bind to extracellular matrix proteins.Infect Immun,2005,73(4):2486-2495
65.Hanna SA,Monteiro da Silva JL,Giannini MJ.Adherence and intracellular parasitism of Paracoccidioides brasiliensis in Vero cells.Microbes Infect,2000,2:877-884
66.Barbosa MS,B(?)o SN,Andreotti PF,et al.Glyceraldehyde-3-phosphate dehydrogenase of Paracoecidioides brasiliensis is a cell surface protein involved in fungal adhesion to extracellular matrix proteins and interaction with cells.Infect Immun,2006,74(1):382-389
67.Pereira LA,B(?)o SN,Barbosa MS,et al.Analysis of the Paracoecidioides brasiliensis triosephosphate isomerase suggests the potential for adhesin function.FEMS Yeast Res,2007,Aug 22;
68.Gaur NK,Klotz SA.Accessibility of the peptide backbone of protein ligands is a key specificity determinant in Candida albicans.SRS adherence.Microbiology,2004,150(Pt 2):277-284
69.Linder M,Szilvay GR,Nakari-Set(a|¨)l(a|¨) T,et al.Surface adhesion of fusion proteins containing the hydrophobins HFBⅠ and HFBⅡ from Trichoderma reesei.Protein Sci,2002,11(9):2257-2266
70.de Groot PW,de Boer AD,Cunningham J,et al.Proteomic analysis ofCandida albicans cell walls reveals covalently bound carbohydrate-active enzymes and adhesins.Eukaryot Cell,2004,3(4):955-965
71.Sandini S,La Valle R,De Bernardis F,et al.The 65 kDa mannoprotein gene of Candida albicans encodes a putative beta-glucanase adhesin required for hyphal morphogenesis and experimental pathogenicity.Cell Microbiol,2007,9(5):1223-1238
72.Munro CA,Bates S,Buurman ET,et al.Mntlp and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and vitulence.J Biol Chem,2005,14;280(2):1051-1060
73.Porcu M,Guarna F,Formentini L,et al.Carboxymethyl beta-glucan binds to corneal epithelial cells and increases cell adhesion to laminin and resistance to oxidative stress.Cornea,2007,26(1):73-79
74.Umeyama T,Kaneko A,Watanabe H,et al.Deletion of the CaBIG1 gene reduces beta-1,6-glucan synthesis,filamentation,adhesion,and virulence in Candida albicans.Infect Immun,2006,74(4):2373-2381
75.Sandovsky-Losica H,Segal E.Infection of HEp2 epithelial cells with Candida albicans:adherence and postadherence events.FEMS Immunol Med Microbiol,2006,46(3):470-475
76.Ibrahim-Granet O,Philippe B,Boleti H,et al.Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages.Infect Immun,2003,71(2):891-903
77.Tsarfaty I,Sandovsky-Losica H,Mittelman L,et al.Cellular actin is affected by interaction with Candida albicans.FEMS Microbiol Lett,2000,189(2):225-232
78.Sherwood J,Gow NA,Gooday GW,et al.Contact sensing in Candida albicans:a possible aid to epithelial penetration.J Med Vet Mycol,1992,30(6):461-469
79.Bailey A,Wadsworth E,Calderone R.Adherence of Candida albicans to human buccal epithelial cells:host-induced protein synthesis and signaling events.Infect Immun,1995,63(2):569-572
80.Blumer K J,Johnson GL.Diversity in function and regulation of MAP kinase pathways.Trends Biochem Sci,1994,19(6):236-240
81.Sandovsky-Losica H,Segal E.Infection of HEp2 epithelial cells with Candida albicans:adherence and postadherence events.FEMS Immunol Med Microbiol,2006,46(3):470-475
82.Kruppa M,Calderone R.Two-component signal transduction in human fungal pathogens.FEMS Yeast Res,2006,6(2):149-159
83.Pott GB,Miller TK,Bartlett JA,et al.The isolation of FOS-1,a gene encoding a putative two-component histidine kinase from Aspergillus fumigatas.Fungal Genet Biol,2000,31(1):55-67
84.Calderone R,Suzuki S,Cannon R,et al.Candida albicans:adherence,signaling and virulence.Med Mycol,2000,38 Suppl 1:125-137
85.Saville SP,Thomas DP,L(?)pez Ribot JL.A role for Efg1p in Candida albicans interactions with extracellular matrices.FEMS Microbiol Lett,2006,256(1):151-158
86.Schaller M,Sch(a|¨)fer W,Korting HC,et al.Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity.Mol Microbiol,1998,29(2):605-615
87.Schaller M,Korting HC,Sch(a|¨)fer W,et al.Secreted aspartie proteinase(Sap) activity contributes to tissue damage in a model of human oral candidosis.Mol Microbiol,1999,34(1):169-180
88.Li D,Bernhardt J,Calderone R.Temporal expression of the Candida albicans genes CHK1and CSSK1,adherence,and morphogenesis in a model of reconstituted human esophageal epithelial candidiasis.Infect lmmun,2002,70(3):1558-1565
89.Chauhan N,Inglis D,Roman E,et al.Candida albicans response regulator gene SSK1regulates a subset of genes whose functions are associated with cell wall biosynthesis and adaptation to oxidative stress.Eukaryot Cell,2003,2(5):1018-1024
90.Calderone R.A,Fonzi WA.Virulence factors of Candida albicans.Trends Microbiol,2001,9(7):327-335
100.Lengeler KB,Davidson RC,D'souza C,et al.Signal transduction cascades regulating fungal development and virulence.Microbiol Mol Biol Rev,2000,64(4):746-785
101.Santoni G,Lucciarini R,Amantini C,et al.Candida albicans expresses a focal adhesion kinase-like protein that undergoes increased tyrosine phosphorylation upon yeast cell adhesion to vitronectin and the EA.hy 926 human endothelial cell line.Infect Immun,2002,70(7):3804-3815
102.Monteiro da Silva JL,Andreotti PF,Benard G.et al.Epithelial cells treated with genistein inhibit adhesion and endocytosis of Paracoccidioides brasiliensis.Antonie Van Leeuwenhoek,2007,92(1):129-135
103.Martinez LR,Casadevall A.Susceptibility of Cryptococcus neoformans biofilms to antifungal agents in vitro.Antimicrob Agents Chemother,2006,50(3):1021-1033
104.Mitchell BM,Wu TG,Jackson BE,et al.Candida albicans strain-dependent virulence and Rim13p-mediated filamentation in experimental keratomycosis.Invest Ophthalmol Vis Sci,2007,48(2):774-780
105.Jackson BE,Wilhelmus KR,Mitchell BM.Genetically regulated filamentation contributes to Candida albicans virulence during corneal infection.Microb Pathog,2007,42(2-3):88-93
106.Mitchell BM,Wu TG.Chong EM,et al.Expression of matrix metalloproteinases 2 and 9 in experimental corneal injury and fungal keratitis.Cornea,2007,26(5):589-593
107.Rohini G,Murugeswari P,Prajna NV,et al.Matrix metalloproteinases(MMP-8,MMP-9)and the tissue inhibitors of metalloproteinases(TIMP-1,TIMP-2) in patients with fungal keratitis.Cornea,2007,26(2):207-211
2.Xie L,Dong X,Shi W.Treatment of fungal keratitis by penetrating keratoplasty.Br J Ophthalmol 2001,85:1070-1074.
3.Xie L,Shi W,Liu Z,et al.Lamellar keratoplasty for the treatment of fungal keratitis.Cornea 2002,21:33-37.
4.Sun,X.G.,Y.Zhang,R.Li,et al.Etiological analysis on ocular fungal infection in the period of 1989-2000.Chin Med J(Engl) 2004,117:598.
5.张文华,潘志强,王智群,等.化脓性角膜溃疡常见致病菌的变迁.中华眼科杂志2002,38:8-12.
6.Tanure MAG,Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea 2000;19:307-312.
7.YanSZ,RodriguesRG,Cahn-HidalgoD,etal.Hemoglobin induces binding of several extracellular matrix proteins to Candida albicans.J Biol Chem,1998,273:5638-5644.
8.Monteiro da Silva JL,Andreotti PF,Benard G,etal.Epithelial cells treated with genistein inhibit adhesion and endocytosis of Paracoccidioides brasiliensis.Antonie Van Leeuwenhoek,2007,92(1):129-135.
9.Dong X,Shi W,Zeng Q,et al.Roles of adherence and matrix metalloprotei- nases in growth patterns of fungal pathogens in cornea.Curr Eye Res.2005 30(8):613-620.
10.Zhong B,Jiang K,Gilvary DL.Human neutrophils utilize a Rac/Cdc42-dependent MAPK pathway to direct intracellular granule mobilization toward ingested microbial pathogens.Blood,2003,101:3240-3248.
11.Whitcher JP,Srinivasan M,Upadhyay MP.Corneal blindness:a global perspective.Bull World Health Organ,2001,79:214-221.
12.Xie L,Dong X,Shi W.Treatment of fungal keratitis by penetrating keratoplasty.Br J Ophthalrnol,2001,85:1070-1074.
13.Gopinathan U,Garg P,Fernandes M,et al.The epidemiological features and laboratory results of fungal keratitis:a 10-year review at a referral eye care centre in South India.Cornea,2002,21:555-559.
14.Chowdhary A,Singh K.Spectrum of Fungal Keratitis in North India.Cornea,2005,24:8-15.
15.Leck AK,Thomas PA,Hagan M,'et al.Aetiology of suppurative corneal ulcers in Ghana and South India,and epidemiology of fungal keratitis.Br J Ophthalmol,2002,86:1211-1215.
16.Upadhyay MP,Karmacharya PC,Koirala S,et al.Epidemiologic characteristics,predisposing factors,and etiologic diagnosis of corneal ulceration in Nepal.Am J Ophthalmol,1991,15:92-99.
17.Gozalbo D,Gil-Navarro I,Azorin I,et al.The cell wall-associated glyceraldehydes-3-phosphate dehydrogenase,of Candida albicans is also a fibronectin and laminin binding protein.Infect Immun,1998,66:2052-2059.
18.Hands SK,Calalb MB,Harper MC,et al.Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin.Proc Natl Acad Sci USA,1992,89(18):8487-8491.
19.Schaller MD,Borgman CA,Cobb BS,et al.pp125 FAK a structurally distinctive protein-tyrosine Icinase associated with focal adhesions.Proc Natl Acad Sci USA,1992,89(11):5192-5196.
20.Schaller MD,Parsons JT.Focal adhesion kinase:an integrin-linked protein tyrosine kinase.Trends Cell Biol,1993,3(8):258-262.
21.Ilic D,Furuta Y,Kanazawa S,et al.Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK deficient mice.Nature,1995,377(6549):539-544.
22.Hecker TP,Gladson CL.Focal adhesion kinase in cancer.Front Biosci,2003,8:S705-S714.
23.Fordin M,Gammeltoft S.Role and regulation of 90 kDa ribosomal S6 kinase(RSK) in signal transduction.Mol Cell Endocrinol,1999,151:65-77.
24.Gonzalez FA,Seth A,Raden DL,et al.Serum-induced translocation of mitogen-activated protein kinase to the cell surface ruffling membrane and the nucleus.J Cell Biol,1993,122:1089-1101.
25.Chen RH,Sarnecki C,Blenis J.Nuclear localization and regulation of the erk- and rsk-encoded protein kinases.Mol Cell Biol,1992,12:915-927.
26.Seger R,Krebs EG.Protein kinases:The Mapk signaling cascade.FASEB J,1995,9,726-735.
27.Sieg DJ,Hauck CR,Ilic D,et al.FAK integrates growth-factor and integrin signals to promote cell migration.Nat Cell Biol,2000,2(5):249-256.
28.Schlaepfer DD,Mitra SK,Ilic D.Control of motile and invasive cell phenoty by focal adhesion kinase.Biochim Biophys Acta,2004,1692(2-3):77-102.
29.Schaller MD.Biochemical signals and biological responses elicited by the focal adhesion kinase.Biochim Biophys Acta,2001,1540(1):1-21.
30.Bin Zhong.Human neutrophils utilize a Rac/Cdc42-dependent MAPK pathway to direct intracellular granule mobilization toward ingested microbial pathogens.Blood,2003,101(8):3240-3248
31.Ningfeng Tang.Inhibition of monocytic interleukin-12 production by candida albicans via selective activation of ERK mitogen-activated protein kinase.Infection and Immunity,2004,72(5):2513-2520
32.Zhong B,Jiang K,Gilvary DL,et al.Human neutrophils utilize a Rac/Cdc42-dependent MAPK pathway to direct intracellular granule mobilization toward ingested microbial pathogens.Blood,2003 101:3240-3248.
33.Sandovsky-Losica H,Segal E.Infection of HEp2 epithelial cells with Candida albicans: adherence and postadherence events.FEMS Immunol Med Microbiol,2006,46(3):470-475
34.Ibrahim-Granet O,Philippe B,Boleti H,et al.Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages.Infect Immun,2003,71(2):891-903
35.Tsarfaty I,Sandovsky-Losica H,Mittelman L,et al.Cellular actin is affected by interaction with Candida albicans.FEMS Microbiol Lett,2000,189(2):225-232
36.Park H,Myers CL,Sheppard DC,et al.Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis.Cell Microbiol,2005,7:499-510
37.Sandovsky-Losica H,Segal E.Infection of HEp2 epithelial cells with Candida albicans:adherence and postadherence events.FEMS Immunol Med Mierobiol,2006,46(3):470-475
38.Kruppa M,Calderone R.Two-component signal transduction in human fungal pathogens.FEMS Yeast Res,2006,6(2):149-159
39.Sandovsky-Losiea H,Berdicevsky I,Tsarfaty I,et al.Effect of Candida albieans metabolites)on cellular actin.FEMS Microbiol Lett,2002;24;215(1):57-62.
40.Tsarfaty I,Sandovsky-Losica H,Mittelman L,et al.Cellular actin is affected by interaction with Candida albicans.FEMS Microbiol Lett 2000,15;189(2):225-232.
41.Ridley AJ,Schwartz,MA,Burridge K,et al.Cell migration:integrating signals from front to bck.Science,2003,302(5651):1704-1709.
42.Degryse B,Orlando S,Resnati M,et al.Urokinase/urokinase receptor and vitronectin/alpha(v)beta(3) integrin induce chemotaxis and cytoskeleton reorganization through different signaling pathways.Oncogene,2001,20(16):2032-2043.
43.Cuevas BD,Abell AN,Witowsky JA,et al.MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts.EMBO J,2003,22(13):3346-3355.
44.Jo M,Thomas KS,Somlyo AV,et al.Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migration.J Biol Chem,2002,277:12479-12485.
45.Webb D J,Nguyen DHD,Gonias SL.Extracellular signal regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and Matrigel invasion.J.Cell Sci,2000,113:123-134.
46.Ridley AJ,Schwartz MA,Burridge K,et al.Cell migration:integrating signals from front to back.Science,2003,3020,1704-1709.
47.Potten CS.Cell replacement in epidermis(keratopoiesis) via discrete units of proliferation.Int Rev Cytol.1981,69:271-318.
48.Tao H,Shimizu M,Kusumoto R,et al.A dual role of FGF10 in proliferation and coordinated migration of epithelial leading edge cells during mouse eyelid development.Development.2005,132(14):3217-3230.
49.Green,Gaudry CA.Are desmosomes more than tethers for intermediate filaments? Nat Rev Mol Cell Biol.2000,1(3):208-216.
50.Usui ML,Underwood RA,Mansbridge JN,et al.Morphological evidence for the role of suprabasal keratinocytes in wound reepithelialization.Wound Repair Regen.2005,13(5):468-479.
51.Radeke HH,Ludwig RJ,Boehncke WH.Experimental approaches to lymphocyte migration in dermatology in vitro and in vivo.Exp Dermatol.2005,14(9):641-666.
52.Gonlugur U,Efeoglu T.Vascular adhesion and transendothelial migration of eosinophil leukoeytes.Cell Tissue Res.2004,318(3):473-482.
53.Sheikine YA,Hansson GK.Chemokines as potential therapeutic targets in atherosderosis.Curr Drug Targets.2006,7(1):13-27.
54.Touyz RM.Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension:role of angiotensin Ⅱ.Exp Physiol.2005,90(4):449-455.
55.von Wichert G,Sheetz MP.Mechanisms of disease:the biophysical interpretation of the ECM affects physiological and pathophysiological cellular behavior.Z Gastroenterol.2005,43(12):1329-1336.
56.Karasarides M,Chiloeches A,Havward R,et al.B-RAF is a therapeutic target in melanoma.Oncogene 2004;23:6292-6298.
57.Itoh RE,Kurokawa K,Ohba Y,et al.Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells.Mol Cell Biol.2002,22(18):6582-6591.
58.Li Z,Hannigan M,Mo Z,et al.Directional sensing requires G beta gamma-mediated PAK1 and PIX alpha-dependent activation of Cdc42.Cell.2003,114(2):215-227.
59.Merlot S,Firtel RA.Leading the way:.Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways.J Cell Sci.2003,116(Pt 17):3471-3478.
60.Katoh H,Negishi M.RhoG activates Racl by direct interaction with the Dockl80-binding protein Elmo.Nature.2003,424(6947):461-464.
61.Cory GO,Ridley AJ.Cell motility:brakingWAVEs.Nature.2002,418(6899):732-733.
62.Snapper SB,Takeshima F,Anton I,et al.N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.Nat Cell Biol.2001,3(10):897-904.
63.Webb DJ,Parsons JT,Horwitz AF.Adhesion assembly,disassembly and turnover in migrating cells-over and over and over again.Nat Cell Biol.2002,4(4):E97-100.
64.Turner CE,West KA,Brown MC.Paxillin-ARF GAP signaling and the cytoskeleton.Curr Opin Cell Biol.2001,13(5):593-599.
65.Brahmbhatt AA,Klemke RL.ERK and RhoA differentially regulate pseudopodia growth and retraction during chemotaxis.J Biol Chem.2003,278(15):13016-13025.
66.Lee J,Ishihara A,Oxford G,et al.Regulation of cell movement is mediated by stretch-activated calcium channels.Nature.1999,400(6742):382-386.
67.Webb DJ,Nguyen D,Gonias SL.Extracellular signal regulated kinase functions in the urokinase receptor-dependent pathway by which neutralization of low density lipoprotein receptor-related protein promotes fibrosarcoma cell migration and Matrigel invasion.J Cell Sci,2000,113,123-134.
68.Klemke RL,Cai S,Criannini AL,et al.Regulation of cell motility by mitogen-activated protein kinase.J Cell Biol,1997,137,481-492.
69.Anand-Apte B,Zetter BR,Viswanathan A,et al.Platelet-derived growth factor and fibronectin-stimulated migration are differentially regulated by the Rac and extracellular signal-regulated kinase pathways.J Biol Chem,1997,272,30688- 30692.
70.Lai CF,Chaudhary L,Fausto A,et al.Erk is essential for growth,differentiation,integrin expression,and cell function in human osteoblastic cells.J Biol Chem,2001,276,14443-14450.
71.Cho SY,Klemke RL.Extracellular-regulated kinase activation and CAS/Crk coupling regulate cell migration and suppress apoptosis during invasion of the extracellular matrix.J Cell Biol,2000,149,223- 236.
72.Cheresh DA,Leng J,Klemke RL.Regulation of cell contraction and membrane ruffling by distinct signals in migratory cells.J Cell Biol,1999,146,1107-1116.
73.Shono T,Kanetake H,Kanda S.The role of mitogen-activated protein kinase activation within focal adhesions in chemotaxis toward FGF- 2 by murine brain capillary endothelial cells.Exp Cell Res,2001,264,275-283.
74.Xie H,Pallero MA,Gupta K,et al.EGF receptor regulation of cell motility:EGF induces disassembly of focal adhesions independently of the motility-associated PLC gamma signaling pathway.J Cell Sci,1998,111,615-624.
75.Guan JL.Role of focal adhesion kinase in integrin signaling.Int J Biochem Cell Biol,1997,29:1085-1096.
76.Hanks SK,Polte TR.Signaling through focal adhesion kinase.Bioessays,1997,19:137-145.
77.Ilic D,Damsky CH,Yamamoto T.Focal adhesion kinase:at the crossroads of signal transduction.J Cell Sci,1997,110:401-407.
78.Schlaepfer DD,Hanck CR,Sieg DJ.Signaling through focal adhesion kinase.Prog Biophys Mol Biol,1999,71:435-478.
79.Zachary I.Focal adhesion kinase.Int J Biochem Cell Biol,1997,29:929-934.
80.王丽娅,张月琴,王印其,等.中国三地区真菌性角膜病致病菌种的调查.中华眼科杂志,2000.36:138-139.
81.谢立信,史伟云,董晓光,等.108例真菌性角膜炎的临床和组织病理学研究.眼科研究,1999.17:283-285.
82.谢立信,李绍伟,史伟云,等.共焦显微镜在真菌性角膜炎临床诊断中的应用.中华眼科杂志,1999,35:7-9.
83.陈瑞娥,戴文丽,孙志坚.真菌性角膜溃疡病原菌及其诱因分析.中华检验医学杂志,2002,25:364
84.Braedel S,Radsak M,Einsele H,et al.Aspergillus fumigatus antigens activate innate immune cells via toll-like receptors 2 and 4.Br J Haematol,2004,125:392-399.
85.Meier A,Kirschning,C.J,Nikolaus T,et al.Toll-like receptor(TLR) 2 and TLR4 are essential for Aspergillus-induoed activation of marine macrophages.Cell Microbiol,2003,5:561-570.
86.Netea MG,Van Der Graaf CA,Vonk AG,et al.The role of toll-like receptor(TLR) 2 and TLR4in the host defense against disseminated candidiasis.J Infect Dis,2002,185:1483-1489.
87.Marnbula SS,Sau K,Henneke P,et al.Toll-like Receptor(TLR) Signaling in Response to Aspergillus fumigatus.J Biol Chem,2002,277:39320-39326.
88.Shoham S,Huang C,Chen JM,et al.Toll-like receptor 4 mediates intracellular signaling without TNF-alpha release in response to Cryptococcus neoformans polysaccharide capsule,J Immunol,2001,166:4620-4626.
89.Villamon E,Gozalbo D,Roig P,et al.Toll-like receptor-2 is essential in marine defenses against Candida albicans infections.Microbes Infect,2004,6:1-7.
90.Sheppard DC,Yeaman MR,Welch WH,et al.Functional and structural diversity in the Als protein family of Candida albicans.J Biol Chem,2004,279(29):30480-30489.
91.Klotz SA,Gaur NK,Lake DF,et al.Degenerate peptide recognition by Candida albieans adhesins Als5p and Als lp.Infect Immun,2004,72(4):2029-2034.
92.Gozalbo D,Gil-Navarro I,Azorin I,et al.The cell wall-associated glyeeraldehydes-3-phosphate dehydrogenase of Candida albicans is also a fibronectin and laminin binding protein.Infect Immun,1998,66:2052-2059.
93.Latge JP.Aspergillus fumigatus and aspergillosis.Clin Mierobiol Rev,1999,12:310-350.
94.Stringaro A,Crateri P,Pellegrini G,et al.Ultrastructural localization of the secretory aspartyl proteinase in Candida albicans cell wall in vitro and in experimentally infected rat vagina.Mycopathologia,1997,137:95-105.
95.Huang G,Zhang M,Erdman SE.Posttranslational modifications required for cell surface localization and function of the fungal adhesin Agalp.Eukaryot Cell,2003,2(5):1099-1114.
96.Calderone R,Suzuki S,Cannon R,et al.Candida albicans:adherence,signaling and virulence.Med Mycol,2000,38 Suppl 1:125-137.
97.Tronchin G,Esnault K,Sanchez M,et al.Purification and partial characterization of a 32-kilodalton sialic acid-specific lectin from Aspergillus fumigatus.Infect immun,2002,70(12):6891-6895.
98.Latg(?) JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev,1999,12(2):310-350.
99.Penalver MC,O' Connor JE,Martinez JP,et al.Binding of human fibronectin to Aspergillus fumigatus conidia[J].Infect Immun,1996,64(4):1146-1153..
100.Kumar CPG,Menon T.Biofilm production by clinical isolate of Candida species.Medical Mycology,2006,44(1):99-10.
101.Al-Fattani MA,Douglas LJ.Penetration of Candida biofilms by antifungal agents.Antimicrob Agents Chemother,2004,48(9):3291-3297.
102.Mitchell BM,Wu TG,Chong EM,et al.Expression of matrix metalloproteinases 2 and 9 in experimental corneal injury and fungal keratitis.Cornea,2007,26(5):589-593.
103.Rohini G,Murugeswari P,Prajna NV,et al.Matrix metalloproteinases(MMP-8,MMP-9) and the tissue inhibitors of metalloproteinases(TIMP-1,TIMP-2) in patients with fungal keratitis.Cornea,2007,26(2):207-211.
104.Monteiro da Silva JL,Andreotti PF,Benard G,et al.Epithelial cells treated with genistein inhibit adhesion and endoeytosis of Paracoccidioides brasiliensis.Antonie Van Leeuwenhoek,2007,92(1):129-135.
105.Jackson BE,Wilhelmus KR,Mitchell BM.Genetically regulated filamentation contributes to Candida albicans virulence during corneal infection.Microb Pathog,2007,42(2-3):88-93.
106.Leidich SD,Ibrahim AS,Fu Y,et al.Cloning and disruption of caPLB1,a phospholipase B gene involved in the pathogenicity ofCandida albicans.J Biol Chem,1998,273:26078-26086.
1.Srinivasan M,Gonzales CA,George C,et al.Epidemiology and aetiological diagnosis of corneal ulceration in Madurai,south India.Br J Ophthalmol 1997,81:965-971
2.Xie L,Dong X,Shi W.Treatment of fungal keratitis by penetrating keratoplasty.Br J Ophthalmol 2001,85:1070-1074
3.Xie L,Shi W,Liu Z,et al.Lamellar keratoplasty for the treatment of fungal keratitis.Cornea 2002,21:33-37
4.Sun,X.G.,Y.Zhang,R.Li,et al.Etiological analysis on ocular fungal infection in the period of 1989-2000.Chin Med J(Engl) 2004,117:598
5.张文华,潘志强,王智群,等.化脓性角膜溃疡常见致病菌的变迁.中华眼科杂志2002,38:8-12
6.Tanure MAG.Cohen EJ,Sudesh S,et al.Spectrum of fungal keratitis at Wills eye hospital,Philadelphia,Pennsylvania.Cornea 2000;19:307-312
7.Chowdhary A,Singh K.Spectrum of Fungal Keratitis in North India.Cornea,2005,24:8-15
8.Rauceo JM,De Armond R,Otoo H,et al.Threonine-rich repeats increase fibronectin binding in the Candida albieans adhesin Als5p.Eukaryot Cell,2006,5(10):1664-1673
9.YanSZ,RodriguesRG.Cahn-HidalgoD,etal.Hemoglobin induces binding of several extracellular matrix proteins to Candida albicans.J Biol Chem,1998,273:5638-5644
10.Monteiro da Silva JL,Andreotti PF,Benard G,etal.Epithelial cells treated with genistein inhibit adhesion and endocytosis of Paracoccidioides brasiliensis.Antonie Van Leeuwenhoek,2007,92(1):129-135
11.HoyerLL,HechtJE.The ALS6 and ALS7 genes of Candida albicans,Yeast,2000,16:847-855
12,FuY,RiegG,Fonzi WA,etal.Expression of the Candida albicans gene ALS1 in Saccharomycescerevisiae induces adherence to endothelial and epithelialcells.InfectImmun,1998,66:1783-1786
13.LozaL,Fu Y,Ibrahim AS,etal.Functional analysis of theCandida albicans ALS1 gene product.Yeast,2004,21:473-482
14.Nobile CJ,Andes DR,Nett JE,et al.Critical role of Bcrl-dependent adhesins in C.albicans biofilm formation in vitro and in vivo.PLoS Pathog,2006,2(7):e63
15.Gaur NK and Klotz SA.Expression,cloning,and characterization of a Candida albicans gene,ALA1,that confers adherence properties upon Saccharomyces cerevisiae for extra cellular matrix proteins.Infect Immun,1997,65(12):5289-5294
16.Gaur NK,Smith RL,Klotz SA.Candida albicans and Saccharomyces cerevisiae expressing ALA1/ALS5 adhere to accessible threonine,serine,or alaninepatches.CellCommun Adhes,2002,9(1):45-57
17.Park H,Myers CL,Sheppard DC,et al.Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis.Cell Microbiol,2005,7:499-510
18.Barki M,Koltin Y,van Wetter M,etal.A Candida albicans surface antigen mediating adhesion and autoaggregation in Saccharomyces cerevisiae.Infect Immun,1994,62(10):4107-4111
19.Staab JF,Sundstrom P.Genetic organization and sequence an alysis of the hypha specific cell wall protein gene HWP 1 of Candida albicans.Yeast,1998,14(7):681- 686
20.Staab JF,Bradway SD,Fidel PL,etal.Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwpl.Science,1999,283(5407):1535-1538
21.Sandini S,La Valle R,De Bernardis F,etal.The 65 kDa mannoprotein gene of Candida albicans encodes a putative beta-glucanase adhesin required for hyphal morphogenesis and experimental pathogenicity,2007,9(5):1223-38
22.Li F,Palecek SP.EAP1,a Candida albicans gene involved in binding human epithelial cells.Eukaryot Cell,2003,2(6):1266-1273
23.Iqraqui I,Carcia-sanchez S,Aubert S,et al The Yaklp ki-nase controls expression of adhesion and biofilm formation inCandida glabrata in 2Sir4p dependentpathway.MolMierobio,12005,55(4):1259-1271
24.Ghannoum MA.Potential role of phospholipase in virulence and fungal pathogenesis.Clin Microbiol Rev,2000,13:122-143
25.Leidich SD,Ibrahim AS,Fu Y,et al.Cloning and disruption of caPLB1,a phospholipase B gene involved in the pathogenicity ofCandida albieans.J Biol Chem,1998,273:26078-26086
26.Iadarola P,Lungarella G,Martorana PA,et al.Lung injury and degradation of extracellular matrix components by Aspergillns fumigatus serine proteinase.Exp Lung Res,1998,24:233-251
27.Tronchin G,Bouchara JP,Larcher G,et al.Interaction between Aspergillus fumigatus and basement membrane laminin:binding and substrate degradation.Biol Cell,1993,77:201-208
28.Iadarola P,Lungarella G,Martorana PA,et al.Lung injury and degradation of extracellular matrix components by Aspergillus fumigatus serine proteinase.Exp Lung Res,1998,24(3):233-251.
29.Dong X,Shi W,Zeng Q,et al.Roles of adherence and matrix metalloprotei- nases in growth patterns of fungal pathogens in cornea.Curt Eye Res.2005 30(8):613-620
30.Yang Q,Su QP,Wang GY,et al.Production of hybrid phage displaying secreted aspartyl proteinase epitope of Candida albicans and its application for the diagnosis of disseminated candidiasis.Mycoses.2007,50(3):165-171
31.Kaur R,Ma B,Cormack BP.A family ofglyeosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata.Proc Natl Acad Sci U S A.2007,104(18):7628-7633
32.Latge JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev,1999,12:310-350
33.Lee JD,Kolattukudy PE.Molecular cloning of the cDNA and gene for an lastinolytic aspartic proteinase from Aspergillus fumigatus and evidence of its secretion by the fungus during invasion of the host lung.Infect Immun,1995,63:3796-3803
34.Tronchin G.Esnault K,Sanchez M,et al.Purification and partial characterization of a 32-kilodalton sialic acid-specific lectin from Aspergillus fumigatus.Infect Immun,2002,70(12):6891-6895
35.Gozalbo D,Gil-Navarro I,Azorin I,et al.The cell wall-associated glyceraldehydes -3-phosphate dehydrogenase of Candida albicans is also a fibronectin and laminin binding protein.Infect Immun,1998,66:2052-2059
36.San-blas G,Travassos LR,Fries BC,et al.Fungal morphogenesis and virulence.Med Myeol,2000,38(Suppl Ⅰ ):79-86
37.Penalver MC,O'Connor JE,Martinez JP,et al.Binding of human fibronectin to Aspergillus fumigatus eonidia[J].Infect Immun,1996,64(4):1146-1153
38.Latg(?) JP.Aspergillus fumigatus and aspergillosis.Clin Microbiol Rev,1999,12(2):310-350
39.Kwan AH,Winefield RD,Sunde M,et al.Structural basis for rodlet assembly in fungal hydrophobins,2006,103(10):3621-3626.
40.Kriznik A,Bouillot M,Coulon J,et al.Morphological specificity of yeast and filamentous Candida albicans forms on surface properties.C R Biol,2005,328(10-11):928-935.
41.Kumar CPG,Menon T.Biofilm production by clinical isolate of Candida species.Medical Mycology,2006,44(1):99-10
42.Kumamoto CA,Vinces MD.Altemative Candida albicans lifesyle:growth on surfaces.Annu Rev Microbial,2005,59:113-133
43.Naglik JR,Challacomber SJ,Hube B.Candida albicans secreted aspartyl proteinases in vim lence and pathogenesis.Microbiol Mol Biol Rev,2003,67(3):400-428
44.Al-Fattani MA,Douglas LJ.Penctration of Candida biofilms by antifungal agents.Antimicrob Agents Chemother,2004,48(9):3291-3297
45.Kukreja N,Arora N,Singh BP,et al.Role of Glycoproteins Isolated from Epicoccum purpurascens in Host-Pathogen Interaction.Patho- biology,2007,74(3):186-192
46.Wang EW,Jung JY,Pashia ME,et al.Otopathogenic Pseudomonas aeruginosa strains as competent biofilm formers.Arch Otolaryng- ol Head Neck Surg,2005,131(11):983-989
47.Rauceo JM,De Armond R,Otoo H,et al.Thrconine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p.Eukaryot Cell,2006,500):1664-1673
48.Rauceo JM,Gaur NK,Lee KG,et al.Global cell surface conformational shift mediated by a Candida albicans adhesin.Infect Immun,2004,72(9):4948-4955
49.Sheppard DC,Yeaman MR,Welch WH,et al.Functional and structural diversity in the Als protein family of Candida albicans.J Biol Chem,2004,279(29):30480-30489
50.Klotz SA,Gaur NK,Lake DF,et al.Degenerate peptide recognition by Candida albicans adhesins Als5p and Als1p.Infect Immun,2004,72(4):2029-2034
51.Sohn K,Seny(u|¨)rek I,Fertey J,et al.An in vitro assay to study the transcriptional response during adherence of Candida albicans to different human epithelia.FEMS Yeast Res,2006,6(7):1085-1093
52.Nobile CJ,Nett JE,Andes DR,et al.Function of Candida albicans adhesin Hwpl in biofilm formation.Eukaryot Cell,2006,5(10):1604-1610
53.Gaur NK,Klotz SA.Accessibility of the peptide backbone of protein ligands is a key specificity determinant in Candida albicans SRS adherence.Microbiology,2004,150(Pt 2):277-284
54.Lee JD,Kolattukudy PE.Molecular cloning of the cDNA and gene for an elastinolytic aspartic proteinase from Aspergillus fumigatus and evidence of its secretion by the fungus during invasion of the host lung.Infect Immun,1995,63(10):3796-3803
55.Ray TL,Payne CD.Scanning electron microscopy of epidermal adherence and cavitation in murine candidiasis:A role for Candida acid proteinase.Infect Immtm,1988,56:1942-1949
56.Stringaro A,Crateri P,Pellegrini G,et al.Ultrastructural localization of the secretory aspartyl proteinase in Candida albicans cell wall in vitro and in experimentally infected rat vagina.Mycopathologia,1997,137:95-105
57.Schaller M,Korting HC,Schafer W,et al.Secreted aspartic proteinase(Sap) activity contributes to tissue damage in a model of human oral candidosis.Mol Microbiol,1999,34:169-180
58.Schaller M,Bein M,Korting HC,et al.The secreted aspartyl proteinases Sap1 and Sap2cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium.Infect Immun,2003,71:3227-3234
59.De Bernardis F,Arancia S,Morelli L,et al.Evidence that members of the secretory aspartyl proteinase gene family,in particular SAP2,are virulence factors for Candida vaginitis.J Infect Dis,1999,179:201-208
60.Andrian E,Grenier D,Rouabhia M.In vitro models of tissue penetration and destruction by Porphyromonas gingivalis.Infect Immun,2004,72:4689-4698
61.Tsai PJ,Kuo CF,Lin KY,et al.Effect of group A streptococcal cysteine protease on invasion of epithelial cells.Infect Immun,1998,66:1460-1466
62.Huang G,Zhang M,Erdman SE.Posttranslational modifications required for cell surface localization and function of the fungal adhesin Agalp.Eukaryot Cell,2003,2(5):1099-1114
63.Calderone R,Suzuki S,Cannon R,et al.Candida albieans:adherence,signaling and virulence.Med Mycol,2000,38 Suppl 1:125-137
64.Gonz(?)lez A,G(?)mez BL,Diez S,et al.Purification and partial characterization of a Paracoccidioides brasiliensis protein with capacity to bind to extracellular matrix proteins.Infect Immun,2005,73(4):2486-2495
65.Hanna SA,Monteiro da Silva JL,Giannini MJ.Adherence and intracellular parasitism of Paracoccidioides brasiliensis in Vero cells.Microbes Infect,2000,2:877-884
66.Barbosa MS,B(?)o SN,Andreotti PF,et al.Glyceraldehyde-3-phosphate dehydrogenase of Paracoecidioides brasiliensis is a cell surface protein involved in fungal adhesion to extracellular matrix proteins and interaction with cells.Infect Immun,2006,74(1):382-389
67.Pereira LA,B(?)o SN,Barbosa MS,et al.Analysis of the Paracoecidioides brasiliensis triosephosphate isomerase suggests the potential for adhesin function.FEMS Yeast Res,2007,Aug 22;
68.Gaur NK,Klotz SA.Accessibility of the peptide backbone of protein ligands is a key specificity determinant in Candida albicans.SRS adherence.Microbiology,2004,150(Pt 2):277-284
69.Linder M,Szilvay GR,Nakari-Set(a|¨)l(a|¨) T,et al.Surface adhesion of fusion proteins containing the hydrophobins HFBⅠ and HFBⅡ from Trichoderma reesei.Protein Sci,2002,11(9):2257-2266
70.de Groot PW,de Boer AD,Cunningham J,et al.Proteomic analysis ofCandida albicans cell walls reveals covalently bound carbohydrate-active enzymes and adhesins.Eukaryot Cell,2004,3(4):955-965
71.Sandini S,La Valle R,De Bernardis F,et al.The 65 kDa mannoprotein gene of Candida albicans encodes a putative beta-glucanase adhesin required for hyphal morphogenesis and experimental pathogenicity.Cell Microbiol,2007,9(5):1223-1238
72.Munro CA,Bates S,Buurman ET,et al.Mntlp and Mnt2p of Candida albicans are partially redundant alpha-1,2-mannosyltransferases that participate in O-linked mannosylation and are required for adhesion and vitulence.J Biol Chem,2005,14;280(2):1051-1060
73.Porcu M,Guarna F,Formentini L,et al.Carboxymethyl beta-glucan binds to corneal epithelial cells and increases cell adhesion to laminin and resistance to oxidative stress.Cornea,2007,26(1):73-79
74.Umeyama T,Kaneko A,Watanabe H,et al.Deletion of the CaBIG1 gene reduces beta-1,6-glucan synthesis,filamentation,adhesion,and virulence in Candida albicans.Infect Immun,2006,74(4):2373-2381
75.Sandovsky-Losica H,Segal E.Infection of HEp2 epithelial cells with Candida albicans:adherence and postadherence events.FEMS Immunol Med Microbiol,2006,46(3):470-475
76.Ibrahim-Granet O,Philippe B,Boleti H,et al.Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages.Infect Immun,2003,71(2):891-903
77.Tsarfaty I,Sandovsky-Losica H,Mittelman L,et al.Cellular actin is affected by interaction with Candida albicans.FEMS Microbiol Lett,2000,189(2):225-232
78.Sherwood J,Gow NA,Gooday GW,et al.Contact sensing in Candida albicans:a possible aid to epithelial penetration.J Med Vet Mycol,1992,30(6):461-469
79.Bailey A,Wadsworth E,Calderone R.Adherence of Candida albicans to human buccal epithelial cells:host-induced protein synthesis and signaling events.Infect Immun,1995,63(2):569-572
80.Blumer K J,Johnson GL.Diversity in function and regulation of MAP kinase pathways.Trends Biochem Sci,1994,19(6):236-240
81.Sandovsky-Losica H,Segal E.Infection of HEp2 epithelial cells with Candida albicans:adherence and postadherence events.FEMS Immunol Med Microbiol,2006,46(3):470-475
82.Kruppa M,Calderone R.Two-component signal transduction in human fungal pathogens.FEMS Yeast Res,2006,6(2):149-159
83.Pott GB,Miller TK,Bartlett JA,et al.The isolation of FOS-1,a gene encoding a putative two-component histidine kinase from Aspergillus fumigatas.Fungal Genet Biol,2000,31(1):55-67
84.Calderone R,Suzuki S,Cannon R,et al.Candida albicans:adherence,signaling and virulence.Med Mycol,2000,38 Suppl 1:125-137
85.Saville SP,Thomas DP,L(?)pez Ribot JL.A role for Efg1p in Candida albicans interactions with extracellular matrices.FEMS Microbiol Lett,2006,256(1):151-158
86.Schaller M,Sch(a|¨)fer W,Korting HC,et al.Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity.Mol Microbiol,1998,29(2):605-615
87.Schaller M,Korting HC,Sch(a|¨)fer W,et al.Secreted aspartie proteinase(Sap) activity contributes to tissue damage in a model of human oral candidosis.Mol Microbiol,1999,34(1):169-180
88.Li D,Bernhardt J,Calderone R.Temporal expression of the Candida albicans genes CHK1and CSSK1,adherence,and morphogenesis in a model of reconstituted human esophageal epithelial candidiasis.Infect lmmun,2002,70(3):1558-1565
89.Chauhan N,Inglis D,Roman E,et al.Candida albicans response regulator gene SSK1regulates a subset of genes whose functions are associated with cell wall biosynthesis and adaptation to oxidative stress.Eukaryot Cell,2003,2(5):1018-1024
90.Calderone R.A,Fonzi WA.Virulence factors of Candida albicans.Trends Microbiol,2001,9(7):327-335
100.Lengeler KB,Davidson RC,D'souza C,et al.Signal transduction cascades regulating fungal development and virulence.Microbiol Mol Biol Rev,2000,64(4):746-785
101.Santoni G,Lucciarini R,Amantini C,et al.Candida albicans expresses a focal adhesion kinase-like protein that undergoes increased tyrosine phosphorylation upon yeast cell adhesion to vitronectin and the EA.hy 926 human endothelial cell line.Infect Immun,2002,70(7):3804-3815
102.Monteiro da Silva JL,Andreotti PF,Benard G.et al.Epithelial cells treated with genistein inhibit adhesion and endocytosis of Paracoccidioides brasiliensis.Antonie Van Leeuwenhoek,2007,92(1):129-135
103.Martinez LR,Casadevall A.Susceptibility of Cryptococcus neoformans biofilms to antifungal agents in vitro.Antimicrob Agents Chemother,2006,50(3):1021-1033
104.Mitchell BM,Wu TG,Jackson BE,et al.Candida albicans strain-dependent virulence and Rim13p-mediated filamentation in experimental keratomycosis.Invest Ophthalmol Vis Sci,2007,48(2):774-780
105.Jackson BE,Wilhelmus KR,Mitchell BM.Genetically regulated filamentation contributes to Candida albicans virulence during corneal infection.Microb Pathog,2007,42(2-3):88-93
106.Mitchell BM,Wu TG.Chong EM,et al.Expression of matrix metalloproteinases 2 and 9 in experimental corneal injury and fungal keratitis.Cornea,2007,26(5):589-593
107.Rohini G,Murugeswari P,Prajna NV,et al.Matrix metalloproteinases(MMP-8,MMP-9)and the tissue inhibitors of metalloproteinases(TIMP-1,TIMP-2) in patients with fungal keratitis.Cornea,2007,26(2):207-211
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |