Candida albicans Hyphal Formation and Virulence Assessed Using a Caenorhabditis elegans Infection Model
Candida albicans Hyphal Formation and Virulence Assessed Using a Caenorhabditis elegans Infection Model
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DOI：
10.1128/ec.00163-09
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发表时间：
2009-11-01
期刊：
影响因子：
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通讯作者：
Mylonakis, Eleftherios
中科院分区：
文献类型：
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作者：
Pukkila-Worley, Read;Peleg, Anton Y.;Mylonakis, Eleftherios
白色念珠菌定植于人类胃肠道，可在易感宿主中引起危及生命的全身感染。我们在这里使用线虫秀丽隐杆线虫在模拟念珠菌病的发病机制系统中研究白色念珠菌毒力决定因素。白色念珠菌的酵母形式被摄入线虫消化道。在液体培养基中，酵母细胞随后发生形态变化，形成菌丝，导致侵袭性组织破坏和线虫死亡。多项证据表明，菌丝形成对于秀丽隐杆线虫中白色念珠菌的发病机制至关重要。首先，在线虫检测中，两种无法形成菌丝的酵母菌种（汉逊德巴利酵母和卢西塔尼亚假丝酵母）的毒性低于白色念珠菌。其次，三种白色念珠菌突变菌株形成菌丝的能力受到损害（efg1 Delta/efg1 Delta、flo8 Delta/flo8 Delta 和 cph1 Delta/cph1 Delta efg1 Delta/efg1 Delta），其毒力显着减弱。第三，条件性tet-NRG1菌株能够对体内形态发生进行外部操作，当在允许菌丝生长的条件下进行测定时，该菌株对秀丽隐杆线虫具有更强的毒性。最后，我们展示了秀丽隐杆线虫测定在筛选白色念珠菌毒力决定簇中的实用性，该测定确定了对体内菌丝形成和杀死秀丽隐杆线虫重要的几个基因，包括最近描述的 CAS5 和 ADA2 基因。这些研究针对秀丽隐杆线虫-C。白色念珠菌感染模型提供了对重要人类病原体毒力机制的深入了解。
Candida albicans colonizes the human gastrointestinal tract and can cause life-threatening systemic infection in susceptible hosts. We study here C. albicans virulence determinants using the nematode Caenorhabditis elegans in a pathogenesis system that models candidiasis. The yeast form of C. albicans is ingested into the C. elegans digestive tract. In liquid media, the yeast cells then undergo morphological change to form hyphae, which results in aggressive tissue destruction and death of the nematode. Several lines of evidence demonstrate that hyphal formation is critical for C. albicans pathogenesis in C. elegans. First, two yeast species unable to form hyphae (Debaryomyces hansenii and Candida lusitaniae) were less virulent than C. albicans in the C. elegans assay. Second, three C. albicans mutant strains compromised in their ability to form hyphae (efg1 Delta/efg1 Delta, flo8 Delta/flo8 Delta, and cph1 Delta/cph1 Delta efg1 Delta/efg1 Delta) were dramatically attenuated for virulence. Third, the conditional tet-NRG1 strain, which enables the external manipulation of morphogenesis in vivo, was more virulent toward C. elegans when the assay was conducted under conditions that permit hyphal growth. Finally, we demonstrate the utility of the C. elegans assay in a screen for C. albicans virulence determinants, which identified several genes important for both hyphal formation in vivo and the killing of C. elegans, including the recently described CAS5 and ADA2 genes. These studies in a C. elegans-C. albicans infection model provide insights into the virulence mechanisms of an important human pathogen.