Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2.
Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2.
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DOI：
10.3390/pathogens4030573
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发表时间：
2015-07-24
期刊：
影响因子：
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通讯作者：
Mitchell AP
中科院分区：
文献类型：
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作者：
Desai JV;Cheng S;Ying T;Nguyen MH;Clancy CJ;Lanni F;Mitchell AP
白色念珠菌RHR 2基因，其指定甘油生物合成酶，是体外和体内生物膜形成所需的。先前的研究表明，RHR2是粘附素基因（如ALS1）表达的最终必需基因。事实上，当ALS1从RHR2非依赖性启动子过表达时，RHR2对于生物膜形成是不必要的。在这里，我们描述了两个额外的生物过程，依赖于RHR2：入侵到非生物基板和致病性在腹部感染模型。我们在这里报告，非生物基质入侵伴随着生物膜的形成，和转录因子突变体的筛选表明，生物膜和菌丝形成能力与入侵能力。然而，本文所呈现的rhr2 Δ/Δ突变体的分析将生物膜形成和侵袭分开。我们发现rhr2 Δ/Δ突变体在粘附素基因ALS 1或转录因子基因BRG 1或UME 6过表达时形成生物膜。然而，生物膜形成菌株不侵入基质。这些结果表明，RHR2在底物侵入中具有粘附素独立的作用，并且数学建模认为RHR2是产生膨压所必需的。以往的研究表明，C.白色念珠菌感染主要表现在两个方面：腹腔脏器感染和持续存在。我们在此报告rhr2 Δ/Δ突变体在这两种感染表型中都有缺陷。我们发现突变体中ALS1的过表达恢复了器官的感染，但并没有改善持续性。因此，RHR2在腹腔感染中具有粘附素非依赖性作用，就像它在基质侵袭中一样。这份报告表明，RHR 2，通过甘油合成，协调与主机或基板的相互作用活动，使C。白色念珠菌种群。
The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population.