Physiologic expression of the Candida albicans pescadillo homolog is required for virulence in a murine model of hematogenously disseminated candidiasis.
Physiologic expression of the Candida albicans pescadillo homolog is required for virulence in a murine model of hematogenously disseminated candidiasis.
复制标题
在血源性念珠菌病小鼠模型中，白色念珠菌同系物的生理表达是其毒力所必需的。
DOI：
10.1128/ec.00171-12
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
LopezRibot,JoseL
中科院分区：
文献类型：
--
作者：
Uppuluri,Priya;Chaturvedi,AshokK;Jani,Niketa;Pukkila-Worley,Read;Monteagudo,Carlos;Mylonakis,Eleftherios;Köhler,JuliaR;LopezRibot,JoseL
Morphogenetic conversions contribute to the pathogenesis of Candida albicans invasive infections. Many studies to date have convincingly demonstrated a link between filamentation and virulence; however, relatively little is known regarding the role of the filament-to-yeast transition during the pathogenesis of invasive candidiasis. We previously identified the C. albicans pescadillo homolog (PES1) as essential during yeast growth and growth of lateral yeast on hyphae but not during hyphal growth. Furthermore, we demonstrated thatPES1is required for virulencein vivoin a Galleria mellonella larva model of candidiasis. Here, we have used a regulatabletetO-PES1/pes1strain to assess the contribution of C. albicansPES1to pathogenesis in the commonly used and clinically relevant murine model of hematogenously disseminated candidiasis. Our results indicate that a physiologically controlled level ofPES1expression is required for full virulence in this animal model, with virulence defects observed both whenPES1is overexpressed and and when it is depleted. The pathogenetic defect of cells depleted ofPES1is not due to a general growth defect, as demonstrated by the fact thatPES1-depleted cells still kill Caenorhabditis elegans as efficiently as the wild type due to hyphal outgrowth through worm tissues. Our results suggest a critical role of lateral yeast growth in the ability of C. albicans to normally proliferate within tissues, as well as a pivotal role for Pes1 in the normal developmental cycle of C. albicans within the mammalian host during infection.
