双联苄化合物riccardin D抗念珠菌生物被膜研究
|
摘要
近年来,由于多种高效、广谱抗菌药物的大量使用,器官移植工作的广泛开展,激素及免疫抑制剂的应用,血液恶性肿瘤患者中抗肿瘤药物的应用,各种人工植入性方法的操作,如人造关节、心脏瓣膜置换、中心静脉插管等,真菌感染的发病率呈逐年增多的趋势。同时,药物的选择性压力迫使微生物产生了多种耐药机制以保证物种的延续,其中,微生物产生生物被膜(biofilm)就是一种重要的耐药机制。植入性器材,比如各种人工假体、血管内插管等常常发生真菌生物被膜感染。微生物形成生物被膜之后,耐药性可发生极为显著的变化,如白色念珠菌(Candida albicans)形成生物被膜之后,对氟康唑的耐药性成倍增加。如何防治和克服C. albicans生物被膜耐药问题,已成为临床上极具挑战性的课题。
天然药物仍然是治疗多种疾病的重要来源。苔藓类植物作为传统药用植物,被应用于多种疾病的治疗,如心血管疾病、支气管炎、皮肤病等,近年来,植物学家从苔藓植物中分离了大量结构新颖且活性显著的萜类和芳香族化合物,其中许多可作为新药研究的优良先导化合物。苔藓类中的地钱属植物为叶状体苔类,从中分离获得的大环双联苄类化合物具有广泛的生物学活性,如抗氧化、抗真菌、抗病毒、抗细菌和细胞毒活性等,具有极高的研究价值。Riccardin D (RCD)是从地钱(Marchantia polymorpha L.(Marchantiaceae))中分离得到的一种大环双联苄类化合物,结构上以C6-C2-C6为母核,通过C-O-C醚桥和(／或)C-C键连接而成。进一步的研究发现,RCD不仅具有抗C. albicans的作用,而且对于C. albicans于体外形成的生物被膜有一定抑制作用,分子机制研究提示,RCD的抗C. albicans生物被膜活性是通过阻碍菌丝形成而实现的。RCD对于C. albicans生物被膜的清除能力、药敏特性,及与其他抗真菌药物联用时是否具协同作用,对于体内形成的生物被膜作用如何,尚需进一步的系统研究。
本课题应用C. albicans生物被膜感染的体外和体内模型,观察了被膜形成不同阶段的形态学特征。应用此模型,研究了念珠菌在形成生物被膜前后对于实验药物RCD单用或与其他抗真菌药物联合应用时的药敏性质特征,比较不同方法用于药敏试验结果评价的适宜性；采用“抗生素封管”给药方法,利用生物被膜体内外模型进行RCD药效学研究,包括药物单用及与氟康唑联合应用时的抗念珠菌效果,应用平板计数法评价试验药物对于体内念珠菌被膜的抑制作用,并采用扫描电镜、激光共聚焦扫描显微镜等方法观察药物作用前后生物被膜的形态学改变；选择菌体黏附与菌丝生长相关基因,制备相应的引物和探针,采用RT-PCR法,考察RCD作用前后有关基因表达的变化,推测RCD抑制念珠菌被膜生长的分子学机制。
课题首先构建了体外载体材料附着生物被膜模型和体内中心静脉插管相关性C. albicans生物被膜感染动物模型,研究了被膜的生长动力学、被膜生长的影响因素与微观形态学特征。在被膜生长前期,菌细胞的含量随时间的延长而明显增多,被膜形成24h时,菌落计数达106CFU,之后生长较前趋于缓慢。被膜生长与菌种和所黏附材料表面特性有关。其微观形态因生长阶段的不同而有明显不同,主要表现在菌体黏附量的多少、菌丝与假菌丝形成及胞外基质等方面的差异。
课题同时研究了C. albicans不同菌株ATCC10231、SC5314、YEM30和CA10在形成被膜前后对于试验药物RCD的敏感性,被膜形成之后,其耐药性增加,增加程度与菌种有关。当RCD与抗真菌药物氟康唑、两性霉素B、卡泊芬净分别联用时,对于各试验菌株形成生物被膜前后有不同程度的增敏作用。药物联用效果以两种方法评价,分别是基于LA理论的FICI法和基于BI理论的△E法,两种方法评价药物抗游离菌作用的结果相符率为75%。
采用抗菌药物封锁试验方法,将不同浓度(8,16,32,64μg/ml)的RCD药液于体外连续作用1、3、5、7日,考察药物对念珠菌成熟生物被膜的清除效果。菌落计数结果证实,RCD对于生长24h的C. albicans生物被膜有抗菌效果,且药物作用时间越长,浓度越高,其抑制被膜生长的强度就越强。以评价被膜中细胞活力为目的的形态学试验亦证明,药物浓度的增加与作用时间的延长可降低被膜中细胞的活力,甚至将被膜完全清除。试验同时考察了RCD与FLC联合应用时对于体外C. albicans生物被膜的抑制作用。结果显示,与FLC单用相比,RCD与FLC联用组生物被膜的菌落计数显著降低,提示RCD对FLC的抗念珠菌生物被膜有增效作用。
课题利用插管相关性念珠菌生物被膜感染动物模型,考察了试验药物对于体内形成的念珠菌生物被膜的药效。模型建立后,在生物被膜形成的不同时段给药,分别考察RCD对于生物被膜的预防和清除作用,应用菌落计数法和形态学观察法进行评价。结果显示,在被膜形成早期(插管感染4h)给予RCD,并在插管内保留8小时,感染24小时后取标本观察,药物可有效预防被膜的形成,与对照组相比,给药组菌量显著降低,其抑菌效应呈剂量依赖性。将RCD与氟康唑联用,可增加后者对于体内被膜形成的预防效果。在插管感染24h时给予不同浓度的RCD,使之在管内每日保留8h,持续作用5日,药物对于生长24h的生物被膜同样有呈剂量依赖性的抑制作用,扫描电镜的微观形态观察证实了菌落计数结果。
为进一步研究RCD于体内外抑制C. albicans生物被膜的内在机制,设计RT-PCR试验,分别取体内和体外试验中RCD作用前后的生物被膜标本,选择与菌体黏附和菌丝生长相关的基因ALS1, ALS3, ECE1, EFG1, HWP1及上游调节基因CDC35进行扩增,并与不加药组标本作对照。对于体内外标本的PCR检测结果表明,RCD作用后,上述基因的表达均呈下调趋势,在体外试验中,以HWP1下调最为显著,体内外结果有较好的一致性。这一结果提示RCD通过抑制菌体黏附和菌丝形成而对C. albicans被膜生长产生抑制作用。
In recent years, the extensive use of efficient and wide-spectrum antimicrobial agents, immunosuppressive agents in organ transplant recipients, antineoplastics in patients with hematologic malignancies, the operation of artificial implantation, such as nearthrosis, heart valve replacement and central venous catheter, contributed to the increasing morbidity associated with fungal infections. The selective pressure of antimicrobials forced microorganisms produced a variety of mechanisms of drug resistance to ensure the continuation of the species, among which biofilms formation is one of the most important drug resistance mechanisms. Fungal biofilms associated infections often occurs when implanting materials are used, such as artificial prosthesis, venous catheters, et al. The susceptibility of microorganisms against antimicrobial agents may change a lot after biofilms formation. For example, Candida albicans biofilms are significantly less susceptible than in planktonic state to antifungals. How to prevent and manage the drug resistance of C. albicans biofilms has become a clinically challenging task.
Natural products are still major sources of innovative therapeutic agents in various conditions. Liverworts have been used in some remedies of folk medicine to treat illnesses of the cardiovascular system, bronchitis and skin diseases as well. In the past decades, various types of lipophilic terpenoids and aromatic compounds showing significant biological activities have been isolated from the bryophytes, some of which can be used as good lead compounds for new drug development. Macrocyclic bis(bibenzyls) compounds isolated from liverworts Marchantia were found to have a wide range of biological activities, such as antioxidation, antifungi, antivirus, antibacteria and cytotoxicity, and have a high value for study. Riccardin D (RCD), a macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L.(Marchantiaceae), structurally consisted of two biphenyl bonds linked by diaryl ether bonds and phenolic hydroxyl groups in different numbers. Further investigation found that RCD had the antifungal effect not only against C. albicans, but against C albicans biofilms formed in vitro. Molecular mechanism study revealed that RCD inhibit C. albicans biofilms via retarding hyphae formation. The biofilms clearance effect, susceptibility property, the antifungal efficacy used with other antifungal agents, and the anti-biofilms formed in vivo need to be further studied.
The study established in vitro and in vivo C. albicans biofilms-associated infective model, and observed the morphology at different developing stages of biofilms growth. Using this model, Candida biofilms formed in vitro and in vivo were studied, including susceptibility property of C. albicans in biofilms or as planktonic cells against RCD when used alone or in combination with other antifungal agents. Different methods were applied to estimate the antifungal effect. RCD solutions at different concentrations were administered locally by using "antibiotics lock technique" to the infective catheters, using quantitative method of colony culture to assess the inhibition efficacy of experimental agents against C. albicans biofilms in vivo. Scanning electron microscopy and confocol laser scanning microscopy were used to evaluate the morphology of C. albicans biofilms before and after drug challenge. Colony culture and morphology observation were used to assess the effect of RCD used alone or in combination with fluconazole on C. albicans biofilms. Quantitative real-time reverse transcription-PCR (RT-PCR) was used to compare mRNA abundances of the genes related to fungal adherence and hypha growth. The TaqMan MGB probe and primer sets were designed for the target genes and the control gene. The molecular mechanism of the inhibition effect of RCD on C. albicans biofilms was speculated according to the change of genes expression before and after RCD challenge.
The study developed in vitro bio-material adherence C. albicans biofilms infective model and CVC-related animal model, and investigated the growth kinetics, impact factors on biofilms development and the micro-morphology properties. During the early phase of biofilms growth, fungal cells increased dramatically. Colony counting was about106CFU when biofilms grew for24h, and afterwards the cell counts increased slowly. Biofilms formation related to the nature of adherence materials and microorganism isolations. Morphology of biofilms changed significantly as time went on, mainly embodied in cell counts, hypha formation and amount of extracellular matrix.
The susceptibility of C. albicans isolates ATCC10231、SC5314、YEM30and CA10in both planktonic and biofilms state against experimental agents was also investigated. Results showed that the resistance of C. albicans increased exponentially after biofilms formation. When RCD were used in combination with fluconazole, amphotericin B or caspofungin, it showed synergistic or indifferent effect against various isolates either in planktonic cells or in biofilms. We applied FICI method based on LA theory and△E method based on BI theory to evaluate the antifungal effect when RCD was used with other agents. The accordance ratio of the two methods was75%when used in assessing the antifungal effect on planktonic cells.
RCD solutions at different concentrations (8,16,32,64μg/ml) were administered to C. albicans biofilms formed in vitro using antibiotic lock technique for1,3,5or7days continuously to investigate the efficacy of anti-biofilms of RCD. Colony counting proved that RCD showed antifungal effect against24-h-old biofilms. The strength of antifungal effect was related to the drug duration and concentrations. Morphology experiment which aimed to assess cell viability also proved that the increase of drug concentration and duration could decrease the cell viability of the biofilms, even some of them was eliminated totally. The anti-biofilms effect of RCD when combined with fluconazole was studied. Results showed that colony counting in combination group decreased significantly than the that challenged by FLC alone, suggesting RCD had hypersensitivity effect to fluconazole against C. albicans biofilms.
Using catheter related C. albicans biofilms infective animal model, the anti-biofilms of experimental drugs. After rabbit model development, RCD solutions were administered at different biofilms formation phase, and evaluated the prevention and therapeutic effect of RCD against C. albicans biofilms. The results were assessed by colony counting and morphology observing. The specimen were taken out after24hours from the initiation of infection. Data showed that RCD could prevent the biofilms formation dose dependently when administered after4h of biofilms growth and maintained in the catheters for8hours. Compared with the control group, colony counting in RCD-challenged group decreased significantly. RCD could increase the prevention effect of fluconazole on C. albicans biofilms according to the results of drug combination experiment. When administered to the24-h-old biofilms at different concentrations and maintained for8hours per day for5days continuously, RCD showed inhibition effect in a dose dependent manner. Micro-morphology observation of scanning electron microscope proved the colony counting results.
We designed RT-PCR experiment to investigate the molecular mechanism of the inhibition effect of RCD against C. albicans biofilms. Specimens of C. albicans biofilms formed in vitro and in vivo were collected and genes related to cells adherence and hypha growth ALS1, ALS3, ECE1, EFG1, HWP1and the upstream regulating gene CDC35were selected and amplified. Biofilms not treated by RCD worked as comparison. Results showed that the genes expression were all down-regulated. The expression of HWP1was decreased most significantly in in vitro study, and there was good accordance between in vitro and in vivo experiment. This suggested that RCD inhibited the biofilms growth via fungal cells adherence and hypha formation.
天然药物仍然是治疗多种疾病的重要来源。苔藓类植物作为传统药用植物,被应用于多种疾病的治疗,如心血管疾病、支气管炎、皮肤病等,近年来,植物学家从苔藓植物中分离了大量结构新颖且活性显著的萜类和芳香族化合物,其中许多可作为新药研究的优良先导化合物。苔藓类中的地钱属植物为叶状体苔类,从中分离获得的大环双联苄类化合物具有广泛的生物学活性,如抗氧化、抗真菌、抗病毒、抗细菌和细胞毒活性等,具有极高的研究价值。Riccardin D (RCD)是从地钱(Marchantia polymorpha L.(Marchantiaceae))中分离得到的一种大环双联苄类化合物,结构上以C6-C2-C6为母核,通过C-O-C醚桥和(／或)C-C键连接而成。进一步的研究发现,RCD不仅具有抗C. albicans的作用,而且对于C. albicans于体外形成的生物被膜有一定抑制作用,分子机制研究提示,RCD的抗C. albicans生物被膜活性是通过阻碍菌丝形成而实现的。RCD对于C. albicans生物被膜的清除能力、药敏特性,及与其他抗真菌药物联用时是否具协同作用,对于体内形成的生物被膜作用如何,尚需进一步的系统研究。
本课题应用C. albicans生物被膜感染的体外和体内模型,观察了被膜形成不同阶段的形态学特征。应用此模型,研究了念珠菌在形成生物被膜前后对于实验药物RCD单用或与其他抗真菌药物联合应用时的药敏性质特征,比较不同方法用于药敏试验结果评价的适宜性；采用“抗生素封管”给药方法,利用生物被膜体内外模型进行RCD药效学研究,包括药物单用及与氟康唑联合应用时的抗念珠菌效果,应用平板计数法评价试验药物对于体内念珠菌被膜的抑制作用,并采用扫描电镜、激光共聚焦扫描显微镜等方法观察药物作用前后生物被膜的形态学改变；选择菌体黏附与菌丝生长相关基因,制备相应的引物和探针,采用RT-PCR法,考察RCD作用前后有关基因表达的变化,推测RCD抑制念珠菌被膜生长的分子学机制。
课题首先构建了体外载体材料附着生物被膜模型和体内中心静脉插管相关性C. albicans生物被膜感染动物模型,研究了被膜的生长动力学、被膜生长的影响因素与微观形态学特征。在被膜生长前期,菌细胞的含量随时间的延长而明显增多,被膜形成24h时,菌落计数达106CFU,之后生长较前趋于缓慢。被膜生长与菌种和所黏附材料表面特性有关。其微观形态因生长阶段的不同而有明显不同,主要表现在菌体黏附量的多少、菌丝与假菌丝形成及胞外基质等方面的差异。
课题同时研究了C. albicans不同菌株ATCC10231、SC5314、YEM30和CA10在形成被膜前后对于试验药物RCD的敏感性,被膜形成之后,其耐药性增加,增加程度与菌种有关。当RCD与抗真菌药物氟康唑、两性霉素B、卡泊芬净分别联用时,对于各试验菌株形成生物被膜前后有不同程度的增敏作用。药物联用效果以两种方法评价,分别是基于LA理论的FICI法和基于BI理论的△E法,两种方法评价药物抗游离菌作用的结果相符率为75%。
采用抗菌药物封锁试验方法,将不同浓度(8,16,32,64μg/ml)的RCD药液于体外连续作用1、3、5、7日,考察药物对念珠菌成熟生物被膜的清除效果。菌落计数结果证实,RCD对于生长24h的C. albicans生物被膜有抗菌效果,且药物作用时间越长,浓度越高,其抑制被膜生长的强度就越强。以评价被膜中细胞活力为目的的形态学试验亦证明,药物浓度的增加与作用时间的延长可降低被膜中细胞的活力,甚至将被膜完全清除。试验同时考察了RCD与FLC联合应用时对于体外C. albicans生物被膜的抑制作用。结果显示,与FLC单用相比,RCD与FLC联用组生物被膜的菌落计数显著降低,提示RCD对FLC的抗念珠菌生物被膜有增效作用。
课题利用插管相关性念珠菌生物被膜感染动物模型,考察了试验药物对于体内形成的念珠菌生物被膜的药效。模型建立后,在生物被膜形成的不同时段给药,分别考察RCD对于生物被膜的预防和清除作用,应用菌落计数法和形态学观察法进行评价。结果显示,在被膜形成早期(插管感染4h)给予RCD,并在插管内保留8小时,感染24小时后取标本观察,药物可有效预防被膜的形成,与对照组相比,给药组菌量显著降低,其抑菌效应呈剂量依赖性。将RCD与氟康唑联用,可增加后者对于体内被膜形成的预防效果。在插管感染24h时给予不同浓度的RCD,使之在管内每日保留8h,持续作用5日,药物对于生长24h的生物被膜同样有呈剂量依赖性的抑制作用,扫描电镜的微观形态观察证实了菌落计数结果。
为进一步研究RCD于体内外抑制C. albicans生物被膜的内在机制,设计RT-PCR试验,分别取体内和体外试验中RCD作用前后的生物被膜标本,选择与菌体黏附和菌丝生长相关的基因ALS1, ALS3, ECE1, EFG1, HWP1及上游调节基因CDC35进行扩增,并与不加药组标本作对照。对于体内外标本的PCR检测结果表明,RCD作用后,上述基因的表达均呈下调趋势,在体外试验中,以HWP1下调最为显著,体内外结果有较好的一致性。这一结果提示RCD通过抑制菌体黏附和菌丝形成而对C. albicans被膜生长产生抑制作用。
In recent years, the extensive use of efficient and wide-spectrum antimicrobial agents, immunosuppressive agents in organ transplant recipients, antineoplastics in patients with hematologic malignancies, the operation of artificial implantation, such as nearthrosis, heart valve replacement and central venous catheter, contributed to the increasing morbidity associated with fungal infections. The selective pressure of antimicrobials forced microorganisms produced a variety of mechanisms of drug resistance to ensure the continuation of the species, among which biofilms formation is one of the most important drug resistance mechanisms. Fungal biofilms associated infections often occurs when implanting materials are used, such as artificial prosthesis, venous catheters, et al. The susceptibility of microorganisms against antimicrobial agents may change a lot after biofilms formation. For example, Candida albicans biofilms are significantly less susceptible than in planktonic state to antifungals. How to prevent and manage the drug resistance of C. albicans biofilms has become a clinically challenging task.
Natural products are still major sources of innovative therapeutic agents in various conditions. Liverworts have been used in some remedies of folk medicine to treat illnesses of the cardiovascular system, bronchitis and skin diseases as well. In the past decades, various types of lipophilic terpenoids and aromatic compounds showing significant biological activities have been isolated from the bryophytes, some of which can be used as good lead compounds for new drug development. Macrocyclic bis(bibenzyls) compounds isolated from liverworts Marchantia were found to have a wide range of biological activities, such as antioxidation, antifungi, antivirus, antibacteria and cytotoxicity, and have a high value for study. Riccardin D (RCD), a macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L.(Marchantiaceae), structurally consisted of two biphenyl bonds linked by diaryl ether bonds and phenolic hydroxyl groups in different numbers. Further investigation found that RCD had the antifungal effect not only against C. albicans, but against C albicans biofilms formed in vitro. Molecular mechanism study revealed that RCD inhibit C. albicans biofilms via retarding hyphae formation. The biofilms clearance effect, susceptibility property, the antifungal efficacy used with other antifungal agents, and the anti-biofilms formed in vivo need to be further studied.
The study established in vitro and in vivo C. albicans biofilms-associated infective model, and observed the morphology at different developing stages of biofilms growth. Using this model, Candida biofilms formed in vitro and in vivo were studied, including susceptibility property of C. albicans in biofilms or as planktonic cells against RCD when used alone or in combination with other antifungal agents. Different methods were applied to estimate the antifungal effect. RCD solutions at different concentrations were administered locally by using "antibiotics lock technique" to the infective catheters, using quantitative method of colony culture to assess the inhibition efficacy of experimental agents against C. albicans biofilms in vivo. Scanning electron microscopy and confocol laser scanning microscopy were used to evaluate the morphology of C. albicans biofilms before and after drug challenge. Colony culture and morphology observation were used to assess the effect of RCD used alone or in combination with fluconazole on C. albicans biofilms. Quantitative real-time reverse transcription-PCR (RT-PCR) was used to compare mRNA abundances of the genes related to fungal adherence and hypha growth. The TaqMan MGB probe and primer sets were designed for the target genes and the control gene. The molecular mechanism of the inhibition effect of RCD on C. albicans biofilms was speculated according to the change of genes expression before and after RCD challenge.
The study developed in vitro bio-material adherence C. albicans biofilms infective model and CVC-related animal model, and investigated the growth kinetics, impact factors on biofilms development and the micro-morphology properties. During the early phase of biofilms growth, fungal cells increased dramatically. Colony counting was about106CFU when biofilms grew for24h, and afterwards the cell counts increased slowly. Biofilms formation related to the nature of adherence materials and microorganism isolations. Morphology of biofilms changed significantly as time went on, mainly embodied in cell counts, hypha formation and amount of extracellular matrix.
The susceptibility of C. albicans isolates ATCC10231、SC5314、YEM30and CA10in both planktonic and biofilms state against experimental agents was also investigated. Results showed that the resistance of C. albicans increased exponentially after biofilms formation. When RCD were used in combination with fluconazole, amphotericin B or caspofungin, it showed synergistic or indifferent effect against various isolates either in planktonic cells or in biofilms. We applied FICI method based on LA theory and△E method based on BI theory to evaluate the antifungal effect when RCD was used with other agents. The accordance ratio of the two methods was75%when used in assessing the antifungal effect on planktonic cells.
RCD solutions at different concentrations (8,16,32,64μg/ml) were administered to C. albicans biofilms formed in vitro using antibiotic lock technique for1,3,5or7days continuously to investigate the efficacy of anti-biofilms of RCD. Colony counting proved that RCD showed antifungal effect against24-h-old biofilms. The strength of antifungal effect was related to the drug duration and concentrations. Morphology experiment which aimed to assess cell viability also proved that the increase of drug concentration and duration could decrease the cell viability of the biofilms, even some of them was eliminated totally. The anti-biofilms effect of RCD when combined with fluconazole was studied. Results showed that colony counting in combination group decreased significantly than the that challenged by FLC alone, suggesting RCD had hypersensitivity effect to fluconazole against C. albicans biofilms.
Using catheter related C. albicans biofilms infective animal model, the anti-biofilms of experimental drugs. After rabbit model development, RCD solutions were administered at different biofilms formation phase, and evaluated the prevention and therapeutic effect of RCD against C. albicans biofilms. The results were assessed by colony counting and morphology observing. The specimen were taken out after24hours from the initiation of infection. Data showed that RCD could prevent the biofilms formation dose dependently when administered after4h of biofilms growth and maintained in the catheters for8hours. Compared with the control group, colony counting in RCD-challenged group decreased significantly. RCD could increase the prevention effect of fluconazole on C. albicans biofilms according to the results of drug combination experiment. When administered to the24-h-old biofilms at different concentrations and maintained for8hours per day for5days continuously, RCD showed inhibition effect in a dose dependent manner. Micro-morphology observation of scanning electron microscope proved the colony counting results.
We designed RT-PCR experiment to investigate the molecular mechanism of the inhibition effect of RCD against C. albicans biofilms. Specimens of C. albicans biofilms formed in vitro and in vivo were collected and genes related to cells adherence and hypha growth ALS1, ALS3, ECE1, EFG1, HWP1and the upstream regulating gene CDC35were selected and amplified. Biofilms not treated by RCD worked as comparison. Results showed that the genes expression were all down-regulated. The expression of HWP1was decreased most significantly in in vitro study, and there was good accordance between in vitro and in vivo experiment. This suggested that RCD inhibited the biofilms growth via fungal cells adherence and hypha formation.
引文
[1]Calderone R. Candida and Candidiasis. ASM Press.2002. Washington DC.
[2]Kojic EM, Darouiche RO. Candida infections of medical devices. Clin Microbiol Rev.2004; 17:255-67.
[3]Douglas LJ. Candida biofilms and their role in infection. Tremds Microbiol. 2003;11(1):30-6.
[4]Lopez-Ribot JL. Candida albicans biofilms:More than filamentation. Curr Biol. 2005; 15:453-5.
[5]Ramage G, Saville SP, Thomas DP, Lopez-Ribot JL. Candida biofilms:An update. Eukaryot Cell.2005; 4:633-8.
[6]Ramage G, Martinez JP, Lopez-Ribot JL. Candida biofilms on implanted biomaterials:A clinically significant problem. FEMS Yeast Res.2006; 6:979-86.
[7]Donlan RM, Costerton JW. Biofilms:survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev.2002; 15(2):167.
[8]Alem MA, Douglas LJ. Prostaglandin production during growth of Candida albicans biofilms. J Med Microbiol.2005; 54:1001-5.
[9]Nett J, Andes D. Candida albicans biofilm development, modeling a host-pathogen interaction. Curr Opin Microbiol.2006; 9:340-5.
[10]Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans:development, architecture, and drug resistance. J Bacteriol.2001; 183(18):5385-94.
[11]Ramage G, Mowat E, Jones B, Williams C, Lopez-Ribot J. Our current understanding of fungal biofilms. Critical Reviews in Microbiology.2009; 35(4): 340-55.
[12]Hawser SP, Douglas LJ. Biofilm formation by Candida species on the surface of catheter materials in vitro. Infect Immun.1994; 62:915-21.
[13]Pierce CG, Uppuluri P, Tristan AR, Wormley Jr FL, Mowat E, Ramage G, Lopez-Ribot JL. A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing. Nat Protoc.2008; 3:1494-500.
[14]Mowat E, Lang S, Williams C, McCulloch E, Jones B, Ramage G. Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms. J Antimicrob Chemother.2008; 62:1281-4.
[15]Hawser SP, Baillie GS, Douglas LJ. Production of extra-cellular matrix by Candida albicans biofilms. J Med Microbiol.1998; 47:253-6.
[16]Schinabeck MK, Long LA, Hossain MA, et al. Rabbit model of Candida albicans biofilm infection:liposomal amphotericin B antifungal lock therapy. Antimicrob Agents Chemother.2004;48(5):1727-32.
[17]Andes D, Nett JE, Oschel P, et al. Development and characterization of an in vivo central venous catheter Candida albicans biofilm model. Infect Immun.2004; 72(10):6023-31.
[18]Nett JE, Lepak AJ, Marchillo K, et al. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis.2009; 200:307-13.
[19]Kumamoto CA, Vinces MD. Alternative Candida albicans Lifestyles:Growth on Surfaces. Annu Rev Microbiol.2005; 59:113-33.
[20]Mukherjee PK, Long L, Kim HG, et al. Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents.2009; 33(2):149-53.
[21]Anna LL, Ashok KC, Christopher GP, et al. Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis. J Antimicrob Chemother.2009; 64:567-70.
[22]Nobile CJ, Nett JE, Hernday AD, et al. Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol.2009; 7(6):e 1000133.
[23]Martinez LR, Mihu MR, Tar M, et al. Demonstration of antibiofilm and antifungal efficacy of chitosan against candidal biofilms, using an in vivo central venous catheter model. J Infect Dis.2010; 201(9):1436-40.
[24]Nett JE, Marchillo K, Spiegel CA, et al. Development and validation of an in vivo Candida albicans biofilm denture model. Infect Immun.2010; 78(9):3650-9.
[25]Dwivedi P, Thompson A, Xie Z, et al. Role of Bcrl-activated genes Hwpl and Hyrl in Candida albicans oral mucosal biofilms and neutrophil evasion. PLoS One. 2011; 6(1):e16218.
[26]Mima EG, Pavarina AC, Dovigo LN, Vergani CE, Costa CA, Kurachi C, Bagnato VS. Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109(3):392-401.
[27]Ricicova M, Kucharikova S, Tournu H, Hendrix J, Bujdakova H, Van Eldere J, Lagrou K, Van Dijck P. Candida albicans biofilm formation in a new in vivo rat model. Microbiology.2010; 156:909-19.
[28]Nailis H, Kucharikova S, Ricicova M, et al. Real-time PCR expression profiling of genes encoding potential virulence factors in Candida albicans biofilms: identification of model-dependent and-independent gene expression. BMC Microbiol.2010; 10:114.
[29]Baillie GS, Douglas LJ. Role of dimorphism in the development of Candida albicans biofilms. J Med Microbiol.1999; 48,671-9.
[30]Garcia-Sanchez S, Aubert S, Iraqui I, Janbon G, Ghigo JM, d'Enfert C. Candida albicans biofilms:A developmental state associated with specific and stable gene expression patterns. Eukaryot Cell.2004; 3:536-45.
[31]Saville SP, Thomas DP, Lopez Ribot JL. A role for Efglp in Candida albicans interactions with extracellular matrices. FEMS Microbiol Lett.2006; 256:151-8.
[32]Sohn K, Urban C, Brunner H, Rupp S. EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays. Mol Microbiol. 2003; 47:89-102.
[33]Li F, Palecek SP. Distinct domains of the Candida albicans adhesin Eaplp mediate cell-cell and cell-substrate interactions. Microbiology.2008; 154:1193-203.
[34]Li F, Svarovsky MJ, Karlsson AJ, Wagner JP, Marchillo K, Oshel P, Andes D, Palecek SP. Eaplp, an adhesin that mediates Candida albicans biofilm formation in vitro and in vivo. Eukaryot Cell.2007; 6:931-9.
[35]Green CB, Cheng G, Chandra J, Mukherjee P, Ghannoum MA, Hoyer LL. RT-PCR detection of Candida albicans ALS gene expression in the reconstituted human epithelium (RHE) model of oral candidiasis and in model biofilms. Microbiology.2004; 150:267-75.
[36]Klotz SA, Gaur NK, De Armond R, Sheppard D, Khardori N, Edwards JE, Jr, Lipke PN, El-Azizi M. Candida albicans Als proteins mediate aggregation with bacteria and yeasts. Med Mycol.2007; 45:363-70.
[37]Nobile CJ, Andes DR, Nett JE, Smith FJ, Yue F, Phan QT, Edwards JE, Filler SG, Mitchell AP. Critical role of Bcrl-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog.2006; 2:e63.
[38]Nobile CJ, Mitchell AP. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcrlp. Curr Biol.2005; 15:1150-5.
[39]Nobile CJ, Nett JE, Andes DR, Mitchell AP. Function of Candida albicans adhesin Hwpl in biofilm formation. Eukaryot Cell.2006; 5:1604-10.
[40]Nobile CJ, Schneider HA, Nett JE, Sheppard DC, Filler SG, Andes DR, Mitchell AP. Complementary adhesin function in C. albicans biofilm formation. Curr Biol. 2008; 18:1017-24.
[41]Hiller E, Heine S, Brunner H, Rupp S. Candida albicans Sun41p, a putative glycosidase, is involved in morphogenesis, cell wall biogenesis, biofilm formation. Eukaryot Cell.2007; 6:2056-65.
[42]Norice CT, Smith Jr FJ, Solis N, Filler SG, Mitchell AP. Requirement for Candida albicans Sun41 in biofilm formation and virulence. Eukaryot Cell.2007; 6:2046-55.
[43]Bates S, Hughes HB, Munro CA, Thomas WP, MacCallum DM, Bertram G, Atrih A, Ferguson MA, Brown AJ, Odds FC, Gow NA. Outer chain N-glycans are required for cell wall integrity and virulence of Candida albicans. J Biol Chem.2006; 281:90-8.
[44]Bates S, MacCallum DM, Bertram G, Munro CA, Hughes HB, Buurman ET, Brown AJ, Odds FC, Gow NA. Candida albicans Pmrlp, a secretory pathway P-type Ca2+/Mn2+-ATPase, is required for glycosylation and virulence. J Biol Chem.2005; 280:23408-15.
[45]Richard ML, Nobile CJ, Bruno VM, Mitchell AP. Candida albicans biofilm-defective mutants. Eukaryot Cell.2005; 4:1493-502.
[46]Kumamoto CA. A contact-activated kinase signals Candida albicans invasive growth and biofilm development. Proc Natl Acad Sci USA.2005;102:5576-81.
[47]Cao YY, Cao YB, Xu Z, Ying K, Li Y, Xie Y, Zhu ZY, Chen WS, Jiang YY. cDNA microarray analysis of differential gene expression in Candida albicans biofilm exposed to farnesol. Antimicrob Agents Chemother.2005; 49:584-9.
[48]Enjalbert B, Whiteway M. Release from quorum-sensing molecules triggers hyphal formation during Candida albicans resumption of growth. Eukaryot Cell. 2005; 4:1203-10.
[49]Yeater KM, Chandra J, Cheng G, Mukherjee PK, Zhao X, Rodriguez-Zas SL, Kwast KE, Ghannoum MA, Hoyer LL. Temporal analysis of Candida albicans gene expression during biofilm development. Microbiology.2007;153:2373-85.
[50]Murillo LA, Newport G, Lan CY, Habelitz S, Dungan J, Agabian NM. Genome-wide transcription profiling of the early phase of biofilm formation by Candida albicans. Eukaryot Cell.2005; 4:1562-73.
[51]Banerjee M, Thompson DS, Lazzell A, Carlisle PL, Pierce C, Monteagudo C, Lopez-Ribot JL, Kadosh D. UME6, a novel filament-specific regulator of Candida albicans hyphal extension and virulence. Mol Biol Cell.2008; 19:1354-65.
[52]Kadosh D, Johnson AD. Induction of the Candida albicans filamentous growth program by relief of transcriptional repression:A genome-wide analysis. Mol Biol Cell.2005; 16:2903-12.
[53]Sohn K, Urban C, Brunner H, Rupp S. EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays. Mol Microbiol. 2003; 47:89-102.
[54]Lepak A, Nett J, Lincoln L, Marchillo K, Andes D. Time course of microbiologic outcome and gene expression in Candida albicans during and following in vitro and in vivo exposure to fluconazole. Antimicrob Agents Chemother.2006; 50:1311-9.
[55]Mukherjee PK, Zhou G, Munyon R, Ghannoum MA. Candida biofilm:A well-designed protected environment. Med Mycol.2005; 43:191-208.
[56]Thomas DP, Bachmann SP, Lopez-Ribot JL. Proteomics for the analysis of the Candida albicans biofilm lifestyle. Proteomics.2006; 6:5795-804.
[57]Vediyappan G, Chaffin WL. Non-glucan attached proteins of Candida albicans biofilm formed on various surfaces. Mycopathologia.2006;161:3-10.
[58]Mukherjee PK, Mohamed S, Chandra J, Kuhn D, Liu S, Antar OS, Munyon R, Mitchell AP, Andes D, Chance MR, Rouabhia M, Ghannoum MA. Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to form a biofilm on catheter surfaces through an ethanol-based mechanism. Infect Immun. 2006; 74:3804-16.
[59]Pierce CG, Thomas DP, Lopez-Ribot JL. Effect of tunicamycin on Candida albicans biofilm formation and maintenance. J Antimicrob Chemother.2009; 63(3):473-9.
[60]陈螟,曹国颖,傅得兴等.棘白素类抗真菌药的研究进展.中国新药杂志.2007;16(14)：1082-3.
[61]吴绍熙,郭宁如.抗真菌药物作用机制的研究进展.四川生理科学杂志.2000；22(4)：17-8.
[62]曹琴,范伟,王凯伟.抗真菌药物的研究进展和临床应用.药学实践杂志.2003;21(4)：225.
[63]王红霞.抗真菌中药研发新进展.黑龙江医药.2006;19(4):310.
[64]于军,苏学今,王丽.射干、金银花等8种中药抗真菌实验研究.军医进修学院学报.2007;28(4)：299.
[65]Mowat E, Butcher J, Lang S, Williams C, Ramage G. Development of a simple model for studying the effects of antifungal agents on multicellular communities of Aspergillus fumigatus. J Med Microbiol.2007; 56:1205-12.
[66]Mah TF, O'Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol.2001; 9:34-9.
[67]Chandra J, Mukherjee PK, Leidich SD, Faddoul FF, Hoyer LL, Douglas LJ, Ghannoum MA. Antifungal resistance of candidal biofilms formed on denture acrylic in vitro. J. Dent. Res.2001; 80:903-8.
[68]Baillie GS, Douglas LJ. Candida biofilms and their susceptibility to antifungal agents. Methods Enzymol.1999; 310:644-56.
[69]Ramage G, Bachmann S, Patterson TF, Wickes BL, Lopez-Ribot JL. Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms. J Antimicrob Chemother.2002; 49:973-980.
[70]Al-Fattani MA, Douglas LJ. Penetration of Candida biofilms by antifungal agents. Antimicrob Agents Chemother.2004; 48:3291-7.
[71]Mukherjee PK, Chandra J, Kuhn DM, Ghannoum MA. Mechanism of azole resistance in Candida albicans biofilms:phase-specific role of efflux pumps and membrane sterols. Infect Immun.2003;71:4333-40.
[72]Ghannoum MA, Rice LB. Antifungal agents:mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev.1999; 12:501-17.
[73]Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K. Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett.2004;230:13-8.
[74]LaFleur MD, Kumamoto CA, Lewis K. Candida albicans biofilms produce antifungal-tolerant persister cells. Antimicrob Agents Chemother.2006;50:3839-46.
[75]Al-Dhaheri RS, Douglas LJ. Absence of amphotericin B-tolerant persister cells in biofilms of some Candida species. Antimicrob Agents Chemother. 2008;52:1884-7.
[76]Baek SH, Phipps RK, Perry NB. Antimicrobial chlorinated bibenzyls from the liverwort riccardia marginata. J Nat Prod.2004;67:718-20.
[77]Lorimer SD, Perry NB. An antifungal bibenzyl from the new Zealand liverwort, Plagiochila stephensoniana. Bioactivity-directed isolation, synthesis and analysis. J Nat Prod.1993;56:1444-50.
[78]Perry NB, Burgess EJ, Baek SH.11-Oxygenated cytotoxic 8,9-secokauranes from a New Zealand liverwort, Lepidolaena taylorii. Phytochemistry.1998; 50(3): 423-33.
[79]Toyota M, Tanimura K, Asakawa Y. Cytotoxic 2,3-secoaro-madendrane type sesquiterpenoids from the liverwort Plagiochila ovalifolia. Planta Med.1998; 64(5): 462-4.
[1]郑璐,余加林,芦起,刘官信.白色念珠菌生物膜体外模型的建立及不同检测方法比较.中国微生态学杂志.2010;22(5):406-10.
[2]Pierce CG, Uppuluri P, Tummala S, Lopez-Ribot JL. A 96 well microtiter plate-based method for monitoring formation and antifungal susceptibility testing of Candida albicans biofilms. J Vis Exp.2010; 44:pii:2287.
[3]Thein ZM, Samaranayake YH, Samaranayake LP. In vitro biofilm formation of Candida albicans and non-albicans Candida species under dynamic and anaerobic conditions. Arch Oral Biol.2007; 52(8):761-7.
[4]Ko KS, Lee JY, Song JH, Peck KR. In vitro Evaluation of Antibiotic Lock Technique for the Treatment of Candida albicans, C. glabrata, and C. tropicalis Biofilms. J Korean Med Sci.2010; 25(12):1722-6.
[5]Schinabeck MK, Long LA, Hossain MA, et al. Rabbit model of Candida albicans biofilm infection:liposomal amphotericin B antifungal lock therapy. Antimicrob Agents Chemother.2004; 48(5):1727-32.
[6]Andes D, Nett JE, Oschel P, et al. Development and characterization of an in vivo central venous catheter Candida albicans biofilm model. Infect Immun.2004; 72(10):6023-31.
[7]Anna LL, Ashok KC, Christopher GP, et al. Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis. J Antimicrob Chemother.2009; 64:567-70.
[8]Kumamoto CA, Vinces MD. Alternative Candida albicans lifestyles:growth on surfaces. Annu Rev Microbiol.2005; 59:113-33.
[9]Mukherjee PK, Long L, Kim HG, et al. Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents.2009; 33(2):149-53.
[10]Nett JE, Lepak AJ, Marchillo K, et al. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis.2009; 200:307-13.
[11]Nobile CJ, Nett JE, Hernday AD, et al. Biofilm matrix regulation by Candida albicans Zapl. PLoS Biol.2009; 7(6):e1000133.
[12]Martinez LR, Mihu MR, Tar M, et al. Demonstration of antibiofilm and antifungal efficacy of chitosan against candidal biofilms, using an in vivo central venous catheter model. J Infect Dis.2010; 201(9):1436-40.
[13]Nett JE, Marchillo K, Spiegel CA, et al. Development and validation of an in vivo Candida albicans biofilm denture model. Infect Immun.2010; 78(9):3650-9.
[14]Dwivedi P, Thompson A, Xie Z, et al. Role of Bcrl-activated genes Hwpl and Hyrl in Candida albicans oral mucosal biofilms and neutrophil evasion. PLoS One. 2011;6(1):e16218.
[15]Mima EG, Pavarina AC, Dovigo LN, Vergani CE, Costa CA, Kurachi C, Bagnato VS. Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109(3):392-401.
[16]Ricicova M, Kucharikova S, et al. Candida albicans biofilm formation in a new in vivo rat model. Microbiology.2010;156:909-19.
[17]Nailis H, Kucharikova S, Ricicova M, et al. Real-time PCR expression profiling of genes encoding potential virulence factors in Candida albicans biofilms: identification of model-dependent and-independent gene expression. BMC Microbiol.2010; 10:114.
[18]徐瑞宏,廖万清.PMT4对新生隐球菌生物膜药物敏感性的影响.中国皮肤性病学杂志.2009;23(11):699-701.
[19]徐瑞宏,方伟,廖万清.新生隐球菌生物膜动物模型构建及PMT4对生物膜形成的影响.中国真菌学杂志.2009;4(4):198-210.
[20]Mermel LA, Farr BM, Sherertz RJ, Raad II, O'Grady N, Harris JS, Craven DE. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis.2001; 32:1249-72.
[21]Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans:development, architecture, and drug resistance. J Bacteriol.2001; 183(18):5385-94.
[1]Pierce CG, Priya U, Tummala S, Lopez-Ribot JL. A 96 Well Microtiter Plate-based Method for Monitoring Formation and Antifungal Susceptibility Testing of Candida albicans Biofilms. Journal of Visualized Experiments,2010.44:p. e2287.
[2]Kucharikova S, Tournu H, Lagrou K, Van Dijck P, Bujdakova H. Detailed comparison of Candida albicans and Candida glabrata biofilms under different conditions and their susceptibility to caspofungin and anidulafungin. J Med Microbiol.2011;60(Pt 9):1261-9.
[3]Ramage G, Vande Walle K, Wickes BL, Lopez-Ribot JL. Standardized Method for In Vitro Antifungal Susceptibility Testing of Candida albicans Biofilms. Antimicrob Agents Chemother.2001; 45(9):p.2475-2479.
[4]朱家馨,张阳隽.卡泊芬净对生物膜态白色念珠菌体外抑菌作用的试验研究.中国药房,2011.22(33):p.3101-3103.
[5]赵今,李继遥,朱晒,周学东,肖晓蓉.口腔多菌种生物膜对防龋中药敏感性的实验研究.华西口腔医学杂志.2006;24(6):546-550.
[6]Schinabeck MK, Hossain MA, Chandra J, Mukherjee PK, Mohamed S, Ghannoum MA. Rabbit Model of Candida albicans Biofilm Infection:Liposomal Amphotericin B Antifungal Lock Therapy. Antimicrob Agents Chemother.2004; 48(5):p.1727-1732.
[7]Tobudic S, Lassnigg A, Graninger W, Presterl E. In vitro activity of antifungal combinations against Candida albicans biofilms. J Antimicrob Chemother,2010.65: p.271-274.
[8]Chatzimoschou A, Katragkou A, Simitsopoulou M, et al. Activities of triazole-echinocandin combinations against Candida species in biofilms and as planktonic cells. Antimicrob Agents Chemother.2011; 55(5):1968-1974.
[9]Zhou Y, Wang G, Li Y, et al. In vitro interactions between aspirin and amphotericin B against planktonic cells and biofilm cells of C. albicans and C. parapsilosis. Antimicrob Agents Chemother.2012.
[1]Mukherjee PK, Long L, Kim HG, Ghannoum MA. Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents.2009; 33(2):149-53.
[2]Messing B, Peitra-Cohen S, Debure A, Beliah M, Bernier JJ. Antibiotic-lock Technique:A new approach to optimal therapy for catheter-related sepsis in home-Parenteral Nutrition Patients. JPEN J Parenter Enteral Nutr.1988; 12(2):185-9.
[3]Cheng A, Sun L, Wu X, Lou H. The inhibitory effect of a macrocyclic bisbibenzyl riccardin D on the biofilms of Candida albicans. Biol Pharm Bull.2009. 32(8):1417-21.
[4]Jones KH, Senft JA. An improved method to determine cell viability by simultaneous staining with fluorescein diacetate-propidium iodide. J Histochem Cytochem.1985; 33(1):77-9.
[5]O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, Lipsett PA, Masur H, Mermel LA, Pearson ML, Raad Ⅱ, Randolph AG, Rupp ME, Saint S; Healthcare Infection ControlPractices Advisory Committee (HICPAC). Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis.2011; 52(9):e162-93.
[6]Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans:development, architecture, and drug resistance. J Bacteriol.2001; 183(18):5385.
[1]Odds FC. Morphogenesis in Candida albicans. Crit Rev Microbiol.1985; 12:45-93.
[2]Leberer E, Harcus D, Dignard D, Johnson L, Ushinsky S, Thomas DY, Schroppel K. Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans. Molecular Microbiology.2001; 42:673-87.
[3]Coleman DA, Zhao X, Zhao H, Hutchins JT, Vernachio JH, Patti JM, Hoyer LL. Monoclonal antibodies specific for Candida albicans Als3 that immunolabel fungal cells in vitro and in vivo and block adhesion to host surfaces. J Microbiol Methods. 2009; 78:71-8.
[4]Hoyer LL, Green CB, Oh SH, Zhao X. Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family-a sticky pursuit. Med Mycol. 2008; 46:1-15.
[5]Zhao X, Daniels KJ, Oh SH, Green CB, Yeater KM, Soil DR, Hoyer LL, Candida albicans Als3p is required for wild-type biofilm formation on silicone elastomer surfaces. Microbiology.2006; 152:2287-99.
[6]Dwivedi P, Thompson A, Xie Z, Kashleva H, Ganguly S, Mitchell AP, Dongari-Bagtzoglou A. Role of Bcrl-activated genes Hwpl and Hyrl in Candida albicans oral mucosal biofilms and neutrophil evasion. PLoS One.2011; 6:e16218. [7] Nobile CJ, Andes DR, Nett JE, Smith FJ, Yue F, Phan QT, Edwards JE, Filler SG, Mitchell AP. Critical role of Bcrl-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog.2006 2:e63.
[8]Nobile CJ, Nett JE, Andes DR, Mitchell AP. Function of Candida albicans adhesin Hwpl in biofilm formation. Eukaryot Cell.2006; 5:1604-1610.
[9]Nett JE, Lepak AJ, Marchillo K, Andes DR. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis.2009; 200(2):307-13.
[2]Kojic EM, Darouiche RO. Candida infections of medical devices. Clin Microbiol Rev.2004; 17:255-67.
[3]Douglas LJ. Candida biofilms and their role in infection. Tremds Microbiol. 2003;11(1):30-6.
[4]Lopez-Ribot JL. Candida albicans biofilms:More than filamentation. Curr Biol. 2005; 15:453-5.
[5]Ramage G, Saville SP, Thomas DP, Lopez-Ribot JL. Candida biofilms:An update. Eukaryot Cell.2005; 4:633-8.
[6]Ramage G, Martinez JP, Lopez-Ribot JL. Candida biofilms on implanted biomaterials:A clinically significant problem. FEMS Yeast Res.2006; 6:979-86.
[7]Donlan RM, Costerton JW. Biofilms:survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev.2002; 15(2):167.
[8]Alem MA, Douglas LJ. Prostaglandin production during growth of Candida albicans biofilms. J Med Microbiol.2005; 54:1001-5.
[9]Nett J, Andes D. Candida albicans biofilm development, modeling a host-pathogen interaction. Curr Opin Microbiol.2006; 9:340-5.
[10]Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans:development, architecture, and drug resistance. J Bacteriol.2001; 183(18):5385-94.
[11]Ramage G, Mowat E, Jones B, Williams C, Lopez-Ribot J. Our current understanding of fungal biofilms. Critical Reviews in Microbiology.2009; 35(4): 340-55.
[12]Hawser SP, Douglas LJ. Biofilm formation by Candida species on the surface of catheter materials in vitro. Infect Immun.1994; 62:915-21.
[13]Pierce CG, Uppuluri P, Tristan AR, Wormley Jr FL, Mowat E, Ramage G, Lopez-Ribot JL. A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing. Nat Protoc.2008; 3:1494-500.
[14]Mowat E, Lang S, Williams C, McCulloch E, Jones B, Ramage G. Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms. J Antimicrob Chemother.2008; 62:1281-4.
[15]Hawser SP, Baillie GS, Douglas LJ. Production of extra-cellular matrix by Candida albicans biofilms. J Med Microbiol.1998; 47:253-6.
[16]Schinabeck MK, Long LA, Hossain MA, et al. Rabbit model of Candida albicans biofilm infection:liposomal amphotericin B antifungal lock therapy. Antimicrob Agents Chemother.2004;48(5):1727-32.
[17]Andes D, Nett JE, Oschel P, et al. Development and characterization of an in vivo central venous catheter Candida albicans biofilm model. Infect Immun.2004; 72(10):6023-31.
[18]Nett JE, Lepak AJ, Marchillo K, et al. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis.2009; 200:307-13.
[19]Kumamoto CA, Vinces MD. Alternative Candida albicans Lifestyles:Growth on Surfaces. Annu Rev Microbiol.2005; 59:113-33.
[20]Mukherjee PK, Long L, Kim HG, et al. Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents.2009; 33(2):149-53.
[21]Anna LL, Ashok KC, Christopher GP, et al. Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis. J Antimicrob Chemother.2009; 64:567-70.
[22]Nobile CJ, Nett JE, Hernday AD, et al. Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol.2009; 7(6):e 1000133.
[23]Martinez LR, Mihu MR, Tar M, et al. Demonstration of antibiofilm and antifungal efficacy of chitosan against candidal biofilms, using an in vivo central venous catheter model. J Infect Dis.2010; 201(9):1436-40.
[24]Nett JE, Marchillo K, Spiegel CA, et al. Development and validation of an in vivo Candida albicans biofilm denture model. Infect Immun.2010; 78(9):3650-9.
[25]Dwivedi P, Thompson A, Xie Z, et al. Role of Bcrl-activated genes Hwpl and Hyrl in Candida albicans oral mucosal biofilms and neutrophil evasion. PLoS One. 2011; 6(1):e16218.
[26]Mima EG, Pavarina AC, Dovigo LN, Vergani CE, Costa CA, Kurachi C, Bagnato VS. Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109(3):392-401.
[27]Ricicova M, Kucharikova S, Tournu H, Hendrix J, Bujdakova H, Van Eldere J, Lagrou K, Van Dijck P. Candida albicans biofilm formation in a new in vivo rat model. Microbiology.2010; 156:909-19.
[28]Nailis H, Kucharikova S, Ricicova M, et al. Real-time PCR expression profiling of genes encoding potential virulence factors in Candida albicans biofilms: identification of model-dependent and-independent gene expression. BMC Microbiol.2010; 10:114.
[29]Baillie GS, Douglas LJ. Role of dimorphism in the development of Candida albicans biofilms. J Med Microbiol.1999; 48,671-9.
[30]Garcia-Sanchez S, Aubert S, Iraqui I, Janbon G, Ghigo JM, d'Enfert C. Candida albicans biofilms:A developmental state associated with specific and stable gene expression patterns. Eukaryot Cell.2004; 3:536-45.
[31]Saville SP, Thomas DP, Lopez Ribot JL. A role for Efglp in Candida albicans interactions with extracellular matrices. FEMS Microbiol Lett.2006; 256:151-8.
[32]Sohn K, Urban C, Brunner H, Rupp S. EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays. Mol Microbiol. 2003; 47:89-102.
[33]Li F, Palecek SP. Distinct domains of the Candida albicans adhesin Eaplp mediate cell-cell and cell-substrate interactions. Microbiology.2008; 154:1193-203.
[34]Li F, Svarovsky MJ, Karlsson AJ, Wagner JP, Marchillo K, Oshel P, Andes D, Palecek SP. Eaplp, an adhesin that mediates Candida albicans biofilm formation in vitro and in vivo. Eukaryot Cell.2007; 6:931-9.
[35]Green CB, Cheng G, Chandra J, Mukherjee P, Ghannoum MA, Hoyer LL. RT-PCR detection of Candida albicans ALS gene expression in the reconstituted human epithelium (RHE) model of oral candidiasis and in model biofilms. Microbiology.2004; 150:267-75.
[36]Klotz SA, Gaur NK, De Armond R, Sheppard D, Khardori N, Edwards JE, Jr, Lipke PN, El-Azizi M. Candida albicans Als proteins mediate aggregation with bacteria and yeasts. Med Mycol.2007; 45:363-70.
[37]Nobile CJ, Andes DR, Nett JE, Smith FJ, Yue F, Phan QT, Edwards JE, Filler SG, Mitchell AP. Critical role of Bcrl-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog.2006; 2:e63.
[38]Nobile CJ, Mitchell AP. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcrlp. Curr Biol.2005; 15:1150-5.
[39]Nobile CJ, Nett JE, Andes DR, Mitchell AP. Function of Candida albicans adhesin Hwpl in biofilm formation. Eukaryot Cell.2006; 5:1604-10.
[40]Nobile CJ, Schneider HA, Nett JE, Sheppard DC, Filler SG, Andes DR, Mitchell AP. Complementary adhesin function in C. albicans biofilm formation. Curr Biol. 2008; 18:1017-24.
[41]Hiller E, Heine S, Brunner H, Rupp S. Candida albicans Sun41p, a putative glycosidase, is involved in morphogenesis, cell wall biogenesis, biofilm formation. Eukaryot Cell.2007; 6:2056-65.
[42]Norice CT, Smith Jr FJ, Solis N, Filler SG, Mitchell AP. Requirement for Candida albicans Sun41 in biofilm formation and virulence. Eukaryot Cell.2007; 6:2046-55.
[43]Bates S, Hughes HB, Munro CA, Thomas WP, MacCallum DM, Bertram G, Atrih A, Ferguson MA, Brown AJ, Odds FC, Gow NA. Outer chain N-glycans are required for cell wall integrity and virulence of Candida albicans. J Biol Chem.2006; 281:90-8.
[44]Bates S, MacCallum DM, Bertram G, Munro CA, Hughes HB, Buurman ET, Brown AJ, Odds FC, Gow NA. Candida albicans Pmrlp, a secretory pathway P-type Ca2+/Mn2+-ATPase, is required for glycosylation and virulence. J Biol Chem.2005; 280:23408-15.
[45]Richard ML, Nobile CJ, Bruno VM, Mitchell AP. Candida albicans biofilm-defective mutants. Eukaryot Cell.2005; 4:1493-502.
[46]Kumamoto CA. A contact-activated kinase signals Candida albicans invasive growth and biofilm development. Proc Natl Acad Sci USA.2005;102:5576-81.
[47]Cao YY, Cao YB, Xu Z, Ying K, Li Y, Xie Y, Zhu ZY, Chen WS, Jiang YY. cDNA microarray analysis of differential gene expression in Candida albicans biofilm exposed to farnesol. Antimicrob Agents Chemother.2005; 49:584-9.
[48]Enjalbert B, Whiteway M. Release from quorum-sensing molecules triggers hyphal formation during Candida albicans resumption of growth. Eukaryot Cell. 2005; 4:1203-10.
[49]Yeater KM, Chandra J, Cheng G, Mukherjee PK, Zhao X, Rodriguez-Zas SL, Kwast KE, Ghannoum MA, Hoyer LL. Temporal analysis of Candida albicans gene expression during biofilm development. Microbiology.2007;153:2373-85.
[50]Murillo LA, Newport G, Lan CY, Habelitz S, Dungan J, Agabian NM. Genome-wide transcription profiling of the early phase of biofilm formation by Candida albicans. Eukaryot Cell.2005; 4:1562-73.
[51]Banerjee M, Thompson DS, Lazzell A, Carlisle PL, Pierce C, Monteagudo C, Lopez-Ribot JL, Kadosh D. UME6, a novel filament-specific regulator of Candida albicans hyphal extension and virulence. Mol Biol Cell.2008; 19:1354-65.
[52]Kadosh D, Johnson AD. Induction of the Candida albicans filamentous growth program by relief of transcriptional repression:A genome-wide analysis. Mol Biol Cell.2005; 16:2903-12.
[53]Sohn K, Urban C, Brunner H, Rupp S. EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays. Mol Microbiol. 2003; 47:89-102.
[54]Lepak A, Nett J, Lincoln L, Marchillo K, Andes D. Time course of microbiologic outcome and gene expression in Candida albicans during and following in vitro and in vivo exposure to fluconazole. Antimicrob Agents Chemother.2006; 50:1311-9.
[55]Mukherjee PK, Zhou G, Munyon R, Ghannoum MA. Candida biofilm:A well-designed protected environment. Med Mycol.2005; 43:191-208.
[56]Thomas DP, Bachmann SP, Lopez-Ribot JL. Proteomics for the analysis of the Candida albicans biofilm lifestyle. Proteomics.2006; 6:5795-804.
[57]Vediyappan G, Chaffin WL. Non-glucan attached proteins of Candida albicans biofilm formed on various surfaces. Mycopathologia.2006;161:3-10.
[58]Mukherjee PK, Mohamed S, Chandra J, Kuhn D, Liu S, Antar OS, Munyon R, Mitchell AP, Andes D, Chance MR, Rouabhia M, Ghannoum MA. Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to form a biofilm on catheter surfaces through an ethanol-based mechanism. Infect Immun. 2006; 74:3804-16.
[59]Pierce CG, Thomas DP, Lopez-Ribot JL. Effect of tunicamycin on Candida albicans biofilm formation and maintenance. J Antimicrob Chemother.2009; 63(3):473-9.
[60]陈螟,曹国颖,傅得兴等.棘白素类抗真菌药的研究进展.中国新药杂志.2007;16(14)：1082-3.
[61]吴绍熙,郭宁如.抗真菌药物作用机制的研究进展.四川生理科学杂志.2000；22(4)：17-8.
[62]曹琴,范伟,王凯伟.抗真菌药物的研究进展和临床应用.药学实践杂志.2003;21(4)：225.
[63]王红霞.抗真菌中药研发新进展.黑龙江医药.2006;19(4):310.
[64]于军,苏学今,王丽.射干、金银花等8种中药抗真菌实验研究.军医进修学院学报.2007;28(4)：299.
[65]Mowat E, Butcher J, Lang S, Williams C, Ramage G. Development of a simple model for studying the effects of antifungal agents on multicellular communities of Aspergillus fumigatus. J Med Microbiol.2007; 56:1205-12.
[66]Mah TF, O'Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol.2001; 9:34-9.
[67]Chandra J, Mukherjee PK, Leidich SD, Faddoul FF, Hoyer LL, Douglas LJ, Ghannoum MA. Antifungal resistance of candidal biofilms formed on denture acrylic in vitro. J. Dent. Res.2001; 80:903-8.
[68]Baillie GS, Douglas LJ. Candida biofilms and their susceptibility to antifungal agents. Methods Enzymol.1999; 310:644-56.
[69]Ramage G, Bachmann S, Patterson TF, Wickes BL, Lopez-Ribot JL. Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms. J Antimicrob Chemother.2002; 49:973-980.
[70]Al-Fattani MA, Douglas LJ. Penetration of Candida biofilms by antifungal agents. Antimicrob Agents Chemother.2004; 48:3291-7.
[71]Mukherjee PK, Chandra J, Kuhn DM, Ghannoum MA. Mechanism of azole resistance in Candida albicans biofilms:phase-specific role of efflux pumps and membrane sterols. Infect Immun.2003;71:4333-40.
[72]Ghannoum MA, Rice LB. Antifungal agents:mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev.1999; 12:501-17.
[73]Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K. Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett.2004;230:13-8.
[74]LaFleur MD, Kumamoto CA, Lewis K. Candida albicans biofilms produce antifungal-tolerant persister cells. Antimicrob Agents Chemother.2006;50:3839-46.
[75]Al-Dhaheri RS, Douglas LJ. Absence of amphotericin B-tolerant persister cells in biofilms of some Candida species. Antimicrob Agents Chemother. 2008;52:1884-7.
[76]Baek SH, Phipps RK, Perry NB. Antimicrobial chlorinated bibenzyls from the liverwort riccardia marginata. J Nat Prod.2004;67:718-20.
[77]Lorimer SD, Perry NB. An antifungal bibenzyl from the new Zealand liverwort, Plagiochila stephensoniana. Bioactivity-directed isolation, synthesis and analysis. J Nat Prod.1993;56:1444-50.
[78]Perry NB, Burgess EJ, Baek SH.11-Oxygenated cytotoxic 8,9-secokauranes from a New Zealand liverwort, Lepidolaena taylorii. Phytochemistry.1998; 50(3): 423-33.
[79]Toyota M, Tanimura K, Asakawa Y. Cytotoxic 2,3-secoaro-madendrane type sesquiterpenoids from the liverwort Plagiochila ovalifolia. Planta Med.1998; 64(5): 462-4.
[1]郑璐,余加林,芦起,刘官信.白色念珠菌生物膜体外模型的建立及不同检测方法比较.中国微生态学杂志.2010;22(5):406-10.
[2]Pierce CG, Uppuluri P, Tummala S, Lopez-Ribot JL. A 96 well microtiter plate-based method for monitoring formation and antifungal susceptibility testing of Candida albicans biofilms. J Vis Exp.2010; 44:pii:2287.
[3]Thein ZM, Samaranayake YH, Samaranayake LP. In vitro biofilm formation of Candida albicans and non-albicans Candida species under dynamic and anaerobic conditions. Arch Oral Biol.2007; 52(8):761-7.
[4]Ko KS, Lee JY, Song JH, Peck KR. In vitro Evaluation of Antibiotic Lock Technique for the Treatment of Candida albicans, C. glabrata, and C. tropicalis Biofilms. J Korean Med Sci.2010; 25(12):1722-6.
[5]Schinabeck MK, Long LA, Hossain MA, et al. Rabbit model of Candida albicans biofilm infection:liposomal amphotericin B antifungal lock therapy. Antimicrob Agents Chemother.2004; 48(5):1727-32.
[6]Andes D, Nett JE, Oschel P, et al. Development and characterization of an in vivo central venous catheter Candida albicans biofilm model. Infect Immun.2004; 72(10):6023-31.
[7]Anna LL, Ashok KC, Christopher GP, et al. Treatment and prevention of Candida albicans biofilms with caspofungin in a novel central venous catheter murine model of candidiasis. J Antimicrob Chemother.2009; 64:567-70.
[8]Kumamoto CA, Vinces MD. Alternative Candida albicans lifestyles:growth on surfaces. Annu Rev Microbiol.2005; 59:113-33.
[9]Mukherjee PK, Long L, Kim HG, et al. Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents.2009; 33(2):149-53.
[10]Nett JE, Lepak AJ, Marchillo K, et al. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis.2009; 200:307-13.
[11]Nobile CJ, Nett JE, Hernday AD, et al. Biofilm matrix regulation by Candida albicans Zapl. PLoS Biol.2009; 7(6):e1000133.
[12]Martinez LR, Mihu MR, Tar M, et al. Demonstration of antibiofilm and antifungal efficacy of chitosan against candidal biofilms, using an in vivo central venous catheter model. J Infect Dis.2010; 201(9):1436-40.
[13]Nett JE, Marchillo K, Spiegel CA, et al. Development and validation of an in vivo Candida albicans biofilm denture model. Infect Immun.2010; 78(9):3650-9.
[14]Dwivedi P, Thompson A, Xie Z, et al. Role of Bcrl-activated genes Hwpl and Hyrl in Candida albicans oral mucosal biofilms and neutrophil evasion. PLoS One. 2011;6(1):e16218.
[15]Mima EG, Pavarina AC, Dovigo LN, Vergani CE, Costa CA, Kurachi C, Bagnato VS. Susceptibility of Candida albicans to photodynamic therapy in a murine model of oral candidosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109(3):392-401.
[16]Ricicova M, Kucharikova S, et al. Candida albicans biofilm formation in a new in vivo rat model. Microbiology.2010;156:909-19.
[17]Nailis H, Kucharikova S, Ricicova M, et al. Real-time PCR expression profiling of genes encoding potential virulence factors in Candida albicans biofilms: identification of model-dependent and-independent gene expression. BMC Microbiol.2010; 10:114.
[18]徐瑞宏,廖万清.PMT4对新生隐球菌生物膜药物敏感性的影响.中国皮肤性病学杂志.2009;23(11):699-701.
[19]徐瑞宏,方伟,廖万清.新生隐球菌生物膜动物模型构建及PMT4对生物膜形成的影响.中国真菌学杂志.2009;4(4):198-210.
[20]Mermel LA, Farr BM, Sherertz RJ, Raad II, O'Grady N, Harris JS, Craven DE. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis.2001; 32:1249-72.
[21]Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans:development, architecture, and drug resistance. J Bacteriol.2001; 183(18):5385-94.
[1]Pierce CG, Priya U, Tummala S, Lopez-Ribot JL. A 96 Well Microtiter Plate-based Method for Monitoring Formation and Antifungal Susceptibility Testing of Candida albicans Biofilms. Journal of Visualized Experiments,2010.44:p. e2287.
[2]Kucharikova S, Tournu H, Lagrou K, Van Dijck P, Bujdakova H. Detailed comparison of Candida albicans and Candida glabrata biofilms under different conditions and their susceptibility to caspofungin and anidulafungin. J Med Microbiol.2011;60(Pt 9):1261-9.
[3]Ramage G, Vande Walle K, Wickes BL, Lopez-Ribot JL. Standardized Method for In Vitro Antifungal Susceptibility Testing of Candida albicans Biofilms. Antimicrob Agents Chemother.2001; 45(9):p.2475-2479.
[4]朱家馨,张阳隽.卡泊芬净对生物膜态白色念珠菌体外抑菌作用的试验研究.中国药房,2011.22(33):p.3101-3103.
[5]赵今,李继遥,朱晒,周学东,肖晓蓉.口腔多菌种生物膜对防龋中药敏感性的实验研究.华西口腔医学杂志.2006;24(6):546-550.
[6]Schinabeck MK, Hossain MA, Chandra J, Mukherjee PK, Mohamed S, Ghannoum MA. Rabbit Model of Candida albicans Biofilm Infection:Liposomal Amphotericin B Antifungal Lock Therapy. Antimicrob Agents Chemother.2004; 48(5):p.1727-1732.
[7]Tobudic S, Lassnigg A, Graninger W, Presterl E. In vitro activity of antifungal combinations against Candida albicans biofilms. J Antimicrob Chemother,2010.65: p.271-274.
[8]Chatzimoschou A, Katragkou A, Simitsopoulou M, et al. Activities of triazole-echinocandin combinations against Candida species in biofilms and as planktonic cells. Antimicrob Agents Chemother.2011; 55(5):1968-1974.
[9]Zhou Y, Wang G, Li Y, et al. In vitro interactions between aspirin and amphotericin B against planktonic cells and biofilm cells of C. albicans and C. parapsilosis. Antimicrob Agents Chemother.2012.
[1]Mukherjee PK, Long L, Kim HG, Ghannoum MA. Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents.2009; 33(2):149-53.
[2]Messing B, Peitra-Cohen S, Debure A, Beliah M, Bernier JJ. Antibiotic-lock Technique:A new approach to optimal therapy for catheter-related sepsis in home-Parenteral Nutrition Patients. JPEN J Parenter Enteral Nutr.1988; 12(2):185-9.
[3]Cheng A, Sun L, Wu X, Lou H. The inhibitory effect of a macrocyclic bisbibenzyl riccardin D on the biofilms of Candida albicans. Biol Pharm Bull.2009. 32(8):1417-21.
[4]Jones KH, Senft JA. An improved method to determine cell viability by simultaneous staining with fluorescein diacetate-propidium iodide. J Histochem Cytochem.1985; 33(1):77-9.
[5]O'Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J, Heard SO, Lipsett PA, Masur H, Mermel LA, Pearson ML, Raad Ⅱ, Randolph AG, Rupp ME, Saint S; Healthcare Infection ControlPractices Advisory Committee (HICPAC). Guidelines for the prevention of intravascular catheter-related infections. Clin Infect Dis.2011; 52(9):e162-93.
[6]Chandra J, Kuhn DM, Mukherjee PK, et al. Biofilm formation by the fungal pathogen Candida albicans:development, architecture, and drug resistance. J Bacteriol.2001; 183(18):5385.
[1]Odds FC. Morphogenesis in Candida albicans. Crit Rev Microbiol.1985; 12:45-93.
[2]Leberer E, Harcus D, Dignard D, Johnson L, Ushinsky S, Thomas DY, Schroppel K. Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans. Molecular Microbiology.2001; 42:673-87.
[3]Coleman DA, Zhao X, Zhao H, Hutchins JT, Vernachio JH, Patti JM, Hoyer LL. Monoclonal antibodies specific for Candida albicans Als3 that immunolabel fungal cells in vitro and in vivo and block adhesion to host surfaces. J Microbiol Methods. 2009; 78:71-8.
[4]Hoyer LL, Green CB, Oh SH, Zhao X. Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family-a sticky pursuit. Med Mycol. 2008; 46:1-15.
[5]Zhao X, Daniels KJ, Oh SH, Green CB, Yeater KM, Soil DR, Hoyer LL, Candida albicans Als3p is required for wild-type biofilm formation on silicone elastomer surfaces. Microbiology.2006; 152:2287-99.
[6]Dwivedi P, Thompson A, Xie Z, Kashleva H, Ganguly S, Mitchell AP, Dongari-Bagtzoglou A. Role of Bcrl-activated genes Hwpl and Hyrl in Candida albicans oral mucosal biofilms and neutrophil evasion. PLoS One.2011; 6:e16218. [7] Nobile CJ, Andes DR, Nett JE, Smith FJ, Yue F, Phan QT, Edwards JE, Filler SG, Mitchell AP. Critical role of Bcrl-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog.2006 2:e63.
[8]Nobile CJ, Nett JE, Andes DR, Mitchell AP. Function of Candida albicans adhesin Hwpl in biofilm formation. Eukaryot Cell.2006; 5:1604-1610.
[9]Nett JE, Lepak AJ, Marchillo K, Andes DR. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis.2009; 200(2):307-13.