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Merck
  • Candida albicans Morphogenesis Programs Control the Balance between Gut Commensalism and Invasive Infection.

Candida albicans Morphogenesis Programs Control the Balance between Gut Commensalism and Invasive Infection.

Cell host & microbe (2019-03-15)
Jessica N Witchley, Pallavi Penumetcha, Nina V Abon, Carol A Woolford, Aaron P Mitchell, Suzanne M Noble
摘要

Candida albicans is a gut commensal and opportunistic pathogen. The transition between yeast and invasive hyphae is central to virulence but has unknown functions during commensal growth. In a mouse model of colonization, yeast and hyphae co-occur throughout the gastrointestinal tract. However, competitive infections of C. albicans homozygous gene disruption mutants revealed an unanticipated, inhibitory role for the yeast-to-hypha morphogenesis program on commensalism. We show that the transcription factor Ume6, a master regulator of filamentation, inhibits gut colonization, not by effects on cell shape, but by activating the expression of a hypha-specific pro-inflammatory secreted protease, Sap6, and a hyphal cell surface adhesin, Hyr1. Like a ume6 mutant, strains lacking SAP6 exhibit enhanced colonization fitness, whereas SAP6-overexpression strains are attenuated in the gut. These results reveal a tradeoff between fungal programs supporting commensalism and virulence in which selection against hypha-specific markers limits the disease-causing potential of this ubiquitous commensal-pathogen.