Genetically regulated filamentation contributes to Candida albicans virulence during corneal infection
Genetically regulated filamentation contributes to Candida albicans virulence during corneal infection
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DOI：
10.1016/j.micpath.2006.11.005
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发表时间：
2007-02-01
影响因子：
3.8
通讯作者：
Mitchell, Bradley M.
中科院分区：
文献类型：
--
作者：
Jackson, Beth E.;Wilhelmus, Kirk R.;Mitchell, Bradley M.
白色念珠菌是正常植物群的共生真菌，但在创伤或手术后以及免疫抑制期间会引起机会性感染。白色念珠菌的毒力因子包括侵入性丝状体的形态发生、对宿主细胞的粘附和蛋白酶的分泌。本研究评价了使用基因改变的酵母菌株的真菌菌丝延伸在实验性白色念珠菌角膜炎中的作用。用野生型（SC 5314）或10种转座子诱导的白色念珠菌突变株局部接种成年BALB/c小鼠的瘢痕角膜，并在接种后（PI）监测4天。还比较了体外生长动力学和酵母菌株出芽成假菌丝或菌丝的能力。野生型人类分离株在小鼠角膜中具有高度的毒力，并且调节粘附或编码膜蛋白的基因缺陷的四种真菌菌株与亲本菌株没有显著差异（P > 0.3）。有5株酵母菌缺失致病基因，导致角膜真菌病完全或部分减毒（P < 0.0001）。野生型和突变株在丰富培养基中的总体生长动力学相似（P > 0.9），但形态发生缺陷的突变株在体外的抑制作用降低。从酵母菌到丝状菌的表型转换促进了实验性白念珠菌角膜疾病的建立和进展。(c)2007爱思唯尔有限公司版权所有。
Candida albicans is a commensal fungus of the normal flora yet causes opportunistic infection following trauma or surgery and during immunosuppression. C albicans virulence factors include morphogenesis into invasive filaments, adherence to host cells, and secretion of proteases. This study evaluated the role of fungal hyphal extension in experimental C albicans keratitis using genetically altered yeast strains. Scarified corneas of adult BALB/c mice were topically inoculated with wild-type (SC5314) or 10 transposon-induced mutant strains of C albicans and monitored for 4 days post inoculation (PI). In vitro growth kinetics and the yeast strains' ability to bud into pseudohyphae or hyphae were also compared. The wild-type human isolate had a high degree of virulence in the murine cornea, and four fungal strains deficient in genes regulating adherence or encoding membrane proteins did not significantly differ from the parental strain (P > 0.3). Five yeast strains deficient in genes involved in filamentation resulted in fully or partially attenuated keratomycosis (P < 0.0001). The overall growth kinetics of wild-type and mutant strains were similar in rich media (P > 0.9), but mutants with deficient morphogenesis had reduced filamentation in vitro. Phenotypic switching from yeasts to filamentous forms facilitates the establishment and progression of experimental corneal disease by C albicans. (c) 2007 Elsevier Ltd. All rights reserved.