Candida antigens involved in site-specific virulence

在我们最初的项目中，我们成功地采用了体内诱导抗原技术（IVIAT）来鉴定59种白色念珠菌基因，这些基因在HIV感染患者的口腔鹅口疮期间优先表达，而在体外生长期间则优先表达。这些在体内诱导的基因中有七个是以前已知的编码念珠菌毒力因子。更重要的是，我们证明了两个以前未被识别的基因，NOT5和IPF15632，编码新的毒力因子。特别值得注意的是，我们发现NOT5对于小鼠口咽和播散性感染期间的正常菌丝形成和完全毒力是必需的。 念珠菌病（分别为OPC和DC）。C.另一方面，白色念珠菌IPF15632编码一种假设的蛋白质，我们证明该蛋白质是OPC期间而不是DC期间毒力所必需的。这些结果表明C.白色念珠菌具有在多个感染部位促成发病的毒力相关基因，以及组织特异性的毒力基因。我们现在将系统地测试我们新发现的几个体内诱导基因在不同组织部位的发病机制中的潜在作用。此外，我们将证明体内诱导基因编码的蛋白质确实存在于念珠菌病期间的不同组织部位。最后，我们将评估不同类型念珠菌病患者体内诱导抗原的抗体应答。

In our original project, we successfully adapted In Vivo Induced Antigen Technology (IVIAT) to identify 59 Candida albicans genes that are preferentially expressed during oral thrush among HIV-infected patients compared to during growth in vitro. Seven of these in vivo induced genes were previously known to encode candida virulence factors. More importantly, we demonstrated that two previously unrecognized genes, NOT5 and IPF15632, encode novel virulence factors. Of particular note, we found that NOT5 is necessary for normal hyphal formation and complete virulence during both murine oropharyngeal and disseminated candidiasis (OPC and DC, respectively). C. albicans IPF15632, on the other hand, encodes a hypothetical protein that we showed to be necessary for virulence during OPC but not DC. These findings suggest that C. albicans possess virulence-associated genes that contribute to pathogenesis at multiple sties of infection, as well as virulence genes that are tissue-specific. We will now systematically test several of our newly identified in vivo induced genes for their potential roles in pathogenesis at diverse tissue sites. In addition, we will demonstrate that the proteins encoded by the in vivo induced genes are indeed present at different tissue sites during candidiasis. Finally, we will assess the antibody responses to in vivo induced antigens among patients with different types of candidiasis.