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Virulence of the Fungal Pathogen Candida albicans Requires the Five Isoforms of Protein Mannosyltransferases

机译:真菌病原性白色念珠菌的毒性需要蛋白质甘露糖基转移酶的五种同工型。

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摘要

The PMT gene family in Candida albicans encodes five isoforms of protein mannosyltransferases (Pmt proteins Pmt1p, Pmt2p, Pmt4p, Pmt5p, and Pmt6p) that initiate O mannosylation of secretory proteins. We compared virulence characteristics of pmt mutants in two complex, three-dimensional models of localized candidiasis, using reconstituted human epithelium (RHE) and engineered human oral mucosa (EHOM); in addition, mutants were tested in a mouse model of hematogenously disseminated candidiasis (HDC). All pmt mutants showed attenuated virulence in the HDC model and at least one model of localized candidiasis. The pmt5 mutant, which lacks in vitro growth phenotypes, was less virulent in the EHOM and HDC assays but had no consistent phenotype in the RHE assay. In contrast, the pmt4 and pmt6 mutants were less virulent in the RHE and HDC assays but not in the EHOM assay. The results stress the contribution of all Pmt isoforms to the virulence of C. albicans and suggest that the importance of individual Pmt isoforms may differ in specific host niches. We propose that Pmt proteins may be suitable targets for future novel classes of antifungal agents.
机译:白色念珠菌中的PMT基因家族编码蛋白质甘露糖基转移酶的五种同工型(Pmt蛋白Pmt1p,Pmt2p,Pmt4p,Pmt5p和Pmt6p),它们会引发分泌型蛋白的甘露糖基化。我们在两种复杂的三维局部念珠菌模型中使用重组人上皮细胞(RHE)和工程人口腔粘膜(EHOM)比较了pmt突变体的毒力特征;此外,在血行播散性念珠菌病(HDC)小鼠模型中测试了突变体。所有的pmt突变体在HDC模型和至少一种局部念珠菌病模型中均显示出减弱的毒力。缺少体外生长表型的pmt5突变体在EHOM和HDC分析中的毒性较低,但在RHE分析中没有一致的表型。相反,在RHE和HDC分析中,pmt4和pmt6突变体的毒性较低,而在EHOM分析中则没有。结果强调了所有Pmt亚型对白色念珠菌的毒性的贡献,并表明单个Pmt亚型的重要性在特定宿主壁host中可能有所不同。我们建议Pmt蛋白可能是未来新型抗真菌剂的合适靶标。

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