马尔尼菲青霉产色与致病力关系的动物实验研究
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摘要
目的：对马尔尼菲青霉(Penicillium marneffei, PM)广西野生银星竹鼠寄生株与临床人分离株在25℃时产色与致病力的关系进行初步探讨。
方法：将15株广西野生银星竹鼠PM寄生株和15株临床人PM分离株在含氯霉素沙氏葡萄糖蛋白胨琼脂液体培养基(SDA液基)25℃震荡培养72h后检测OD值,代表不同菌株产红色素的色价。分别筛选出OD值最大、中位数及最小的各3株菌株。用筛选出菌株的菌悬液经腹腔注射途径感染健康昆明小鼠。观察接种后各组小鼠不同时期的一般情况、脏器感染情况、主要脏器病理组织学改变、生存时间及生存率,检测不同时期小鼠肝脏菌载量计数。6周后将剩余小鼠全部处死,观察主要脏器病变程度,计算小鼠肝脏菌载量并进行统计学分析。
结果：两种不同来源的PM在SDA液基25℃培养72h后均产生可溶性、不同程度的红色色素。野生株和临床株PM产色OD值分别为0.885±0.722,0.837±0.713,用计量资料两独立样本t检验进行统计学分析,两种不同来源PM产色无差异(P>0.05)。被感染小鼠的发病率均为100%。不同OD值组小鼠内脏病变程度、肝组织菌载量、生存率有差异,且菌株OD值越大其内脏病变程度越严重,肝脏菌载量越高,小鼠生存率越低。两种不同来源的PM内脏病变程度、肝组织菌载量、生存率无差异(P>0.05)。
结论：PM在25℃所产生的红色色素是其重要的毒力标志；竹鼠寄生株PM与临床人感染株PM在25℃时产色能力无差异；两种不同来源的PM动物实验其致病力无差异。
Objective preliminary study the relationship between red pigment and pathogencity of Penicillium marneffei.
Method15isolates from Guang Xi Bamboo rats isolates and15patients isolates were selected and cultured in SDA liquid25℃for72hours, and then the OD values were acquired, represent the pigment Select the maximum, median, minimum isolates, in which the suspension was injected into normal mice from abdominal. Observe the general status, infection status of internal organs. Mice survival after infection and colony count of liver in mice were calculated. And Six weeks later the remaining mice all executed, also observe the infection status of internal organs, calculate colony count of liver and carries on statistics analysis.
Results It is demonstrated that all30isolates could produced red pigment in different levels, while there was no significant difference in statistics between two different sources of PM(P<0.05). There was different infection status of internal organs, survival and colony count of liver in different groups of OD value, and then the higher of the OD value, the more serious of the internal organs infection and the colony count of liver, at the same time the lower of the survival rate.
Conclusion The red pigment in25℃which probably involved in the Virulence markers. There was no significant difference of the red pigment between two different sources of PM. There is not significant difference of pathogenicity between PM isolated from bamboo rats and patients.
方法：将15株广西野生银星竹鼠PM寄生株和15株临床人PM分离株在含氯霉素沙氏葡萄糖蛋白胨琼脂液体培养基(SDA液基)25℃震荡培养72h后检测OD值,代表不同菌株产红色素的色价。分别筛选出OD值最大、中位数及最小的各3株菌株。用筛选出菌株的菌悬液经腹腔注射途径感染健康昆明小鼠。观察接种后各组小鼠不同时期的一般情况、脏器感染情况、主要脏器病理组织学改变、生存时间及生存率,检测不同时期小鼠肝脏菌载量计数。6周后将剩余小鼠全部处死,观察主要脏器病变程度,计算小鼠肝脏菌载量并进行统计学分析。
结果：两种不同来源的PM在SDA液基25℃培养72h后均产生可溶性、不同程度的红色色素。野生株和临床株PM产色OD值分别为0.885±0.722,0.837±0.713,用计量资料两独立样本t检验进行统计学分析,两种不同来源PM产色无差异(P>0.05)。被感染小鼠的发病率均为100%。不同OD值组小鼠内脏病变程度、肝组织菌载量、生存率有差异,且菌株OD值越大其内脏病变程度越严重,肝脏菌载量越高,小鼠生存率越低。两种不同来源的PM内脏病变程度、肝组织菌载量、生存率无差异(P>0.05)。
结论：PM在25℃所产生的红色色素是其重要的毒力标志；竹鼠寄生株PM与临床人感染株PM在25℃时产色能力无差异；两种不同来源的PM动物实验其致病力无差异。
Objective preliminary study the relationship between red pigment and pathogencity of Penicillium marneffei.
Method15isolates from Guang Xi Bamboo rats isolates and15patients isolates were selected and cultured in SDA liquid25℃for72hours, and then the OD values were acquired, represent the pigment Select the maximum, median, minimum isolates, in which the suspension was injected into normal mice from abdominal. Observe the general status, infection status of internal organs. Mice survival after infection and colony count of liver in mice were calculated. And Six weeks later the remaining mice all executed, also observe the infection status of internal organs, calculate colony count of liver and carries on statistics analysis.
Results It is demonstrated that all30isolates could produced red pigment in different levels, while there was no significant difference in statistics between two different sources of PM(P<0.05). There was different infection status of internal organs, survival and colony count of liver in different groups of OD value, and then the higher of the OD value, the more serious of the internal organs infection and the colony count of liver, at the same time the lower of the survival rate.
Conclusion The red pigment in25℃which probably involved in the Virulence markers. There was no significant difference of the red pigment between two different sources of PM. There is not significant difference of pathogenicity between PM isolated from bamboo rats and patients.
引文
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[3]Disalvo DA, Fickling AM, Ajello L, Infection caused by Penicillium marneffei[J]. Description of first natural infection in man Am JC lin PAthol,1973,60(2):259-263.
[4]李菊裳,潘乐泉,邓卓霖等.马尔尼菲青霉病一例报告[J].临床皮肤科杂志,1985,14：24-26.
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[2]梁伶,成先桂,刘栋华,等.马尔尼菲青霉菌野生株和临床分离株致病力研究[J].中国人兽共患病学报,2008,24(3)：240-242.
[3]李民,杨连娟,涂宏刚,等.小鼠播散性马尔尼菲青霉菌感染模型的建立及其生存率分析[J].中国皮肤性病学杂志,2010,24(6)：512-514.
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[2]Segretain G, Penicillium marneffei n. sp, agent of amycosis of the reticuloendothelial systerm[J]. Mycopathologia,1959,30(11):327-353.
[3]Disalvo DA, Fickling AM, Ajello L, Infection caused by Penicillium marneffei[J]. Description of first natural infection in man Am JC lin PAthol,1973,60(2):259-263.
[4]李菊裳,潘乐泉,邓卓霖等.马尔尼菲青霉病一例报告[J].临床皮肤科杂志,1985,14：24-26.
[5]Supparatp inyo K, Khamwan C, Baosoung V, et al Disseminated Penicillium marneffei infection in southeast Asia[J]. Lancet, 1994,344(8915):110-113
[6]梁伶,李菊裳.马尔尼菲青霉的生态学研究[J].广西医科大学学报,1999,16：602-604.
[7]梁伶,成先桂,刘栋华,等.马尔尼菲青霉菌野生株和临床分离株致病力研究[J].中国人兽共患病学报,2008,24：240-242.
[8]Donghua Liu, Ling Liang, Qiuhong Luo,et al. Morphology of Penicillium marneffei under oxidative stress in vitro [J]. Mycoses, 2009,54:113-118.
[9]Cunwei Cao, Ling Liang, Wenjuan Wang, et al. Common Reservoirs for Penicillium marneffei Infection in Humans and Rodents, China, Emerging infectious diseases[J].2011,17:209-214.
[10]Nosanchuk JD. Clinical impact of fungal melanisation. The Congress Handbook & Abstract Book 2 of The 8th International Mycological Congress in Cairns, Australia on August 20-25,2006:264.
[11]Dixon DM, Polak A, Szaniszlo PJ. Pathogenicity and virulence of wild-type and melanin-dficient Wangiella dermatitidis[J].J Med Vet Mycol 25,97-106.
[12]Casadevall A, Rosas A L, Nosanchuk J D. Melanin and virulence in Cryptococcus neoformans[J]. Cuff Opin Microbiol 3:354-358.
[13]Youngchim S, Hay RJ, Hamilton AJ. Melanization of Penicillium marneffei in vitro and in vivo[J]. Microbiology,2005, 151(1):291-299.
[14]刘栋华,谭升顺,罗红等,氟康唑诱导菌丝相马尔尼菲青霉菌产67.5kDa蛋白[J].中国皮肤性病学杂志,2006,20(12)：718-720.
[15]陈义光,彭德娇,田宏现。红曲及红曲霉的研究与应用[J].湖北农学院学报(自然科学版),2000,20(2)：188-190.
[16]马韵,邓卓霖,李山,等.马尔尼菲青霉不同菌株的免疫原性和致病力研究[J].广西医科大学学报,1994,11：128-130.
[17]Wong KH, Lee SS, Chan KC. Twenty years of clinical human immunodeficiency virus(HIV) and acquired immunodeficiency syndrome(AIDS) in Hong Kong[J]. Hong Kong Med J, 2006,12(2):133-140.
[18]Cooper CR, Vanittanakom N. Insights into the pathogenicity of Penicillium marneffei[J]. Future Microbiol,2008,3(1):43-55.
[19]唐志荣,刘伟,陈杰,等.广西艾滋病例合并马尔尼菲青霉菌感染及其治疗[J].应用预防医学,2007,13(1)：28-29.
[20]Dadachova E, Bryan RA, Huang X, et al. Ionizing radiation changes the electronic properties of melanin and enhances the growth of melanized fungi[J]. PLoSONE,2007,2(5):457.
[21]Patrick CY Woo, Emily WT Tam, Ken TK Chong, et al. High diversity of polyketide synthase genes and the melanin biosynthesis gene cluster in Penicillium marneffei[J]. The FEBS Journal,2010,277(18):3750-3758.
[22]庄晓晟,梁伶,曹存巍,等.马尔尼菲青霉产色与gasC基因表达关系研究[J].中国人畜共患病学报,2010,26(4)：341-348.
[23]Kudeken N, Kawakami K, Saito A. CD4+ T cell mediated fatal hyperinflalmmatory reactions in mice infected with Penicillium marneffei[J]. Clin Exp Immunol.1997,107:468-473.
[24]Cui J, Tanaka R, Taguchi H, et al. Histopathological and electron microscopical studies on experimental Penicillium marneffei infection in mice[J]. Journal of Medical & Veterinary Mycology,1997,35(5):347-353.
[25]刘栋华,谭升顺,梁伶,等.经皮肤损伤感染马尔尼菲青霉菌致病力动物实验研究[J].中国皮肤性病学杂志,2006,20(6)：324-326.
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