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 disseminatedcandidiasis (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.
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