Self-Regulation of Candida albicans Population Size during GI Colonization

Department of Molecular Biology and Microbiology, Tufts University, Boston, Massachusetts, United States of America.
PLoS Pathogens (Impact Factor: 7.56). 01/2008; 3(12):e184. DOI: 10.1371/journal.ppat.0030184
Source: PubMed


Interactions between colonizing commensal microorganisms and their hosts play important roles in health and disease. The opportunistic fungal pathogen Candida albicans is a common component of human intestinal flora. To gain insight into C. albicans colonization, genes expressed by fungi grown within a host were studied. The EFH1 gene, encoding a putative transcription factor, was highly expressed during growth of C. albicans in the intestinal tract. Counterintuitively, an efh1 null mutant exhibited increased colonization of the murine intestinal tract, a model of commensal colonization, whereas an EFH1 overexpressing strain exhibited reduced colonization of the intestinal tract and of the oral cavity of athymic mice, the latter situation modeling human mucosal candidiasis. When inoculated into the bloodstream of mice, both efh1 null and EFH1 overexpressing strains caused lethal infections. In contrast, other mutants are attenuated in virulence following intravenous inoculation but exhibited normal levels of intestinal colonization. Finally, although expression of several genes is dependent on transcription factor Efg1p during laboratory growth, Efg1p-independent expression of these genes was observed during growth within the murine intestinal tract. These results show that expression of EFH1 regulated the level of colonizing fungi, favoring commensalism as opposed to candidiasis. Also, different genes are required in different host niches and the pathway(s) that regulates gene expression during host colonization can differ from well-characterized pathways used during laboratory growth.

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    • "To achieve efficient gastrointestinal colonization, this fungus possesses complicated adaptation capacities to sense host niches, adhere to the host mucosal surface and successfully colonize this unique environment. All of these capacities are also related to morphogenetic processes (White et al., 2007). Therefore, strategies that inhibit morphogenesis of this fungus may also have an impact on relevant physiological processes, such as adhesion, colonization and invasion of host tissues, and may be used for antifungal drugs against its infections. "
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    • "An unbalanced microflora and a malfunctioning immune system are unable to control the C. albicans population size and the host becomes susceptible to candidiasis (Macphail et al., 2002; Perlroth et al., 2007). In these situations, the fungal burden increases and various environmental cues, such as nutrient availability, pH, and temperature stimulate hypha formation (Biswas et al., 2007; Whiteway and Bachewich, 2007; Shapiro and Cowen, 2010; Sudbery, 2011). This may lead to life-threatening infections where the fungi disseminate to different internal organs (Macphail et al., 2002; Pfaller and Diekema, 2007). "
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