Self-Regulation of Candida albicans Population Size during GI Colonization

Abstract

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.

Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation

“…The human gastrointestinal (GI) tract is colonized with trillions of commensal microbes, including Candida species. Interestingly, C. albicans stays mostly as the yeast form in the GI tract (42). Farnesol may play a role, because the cup9 mutant displayed slightly increased colonization in the GI tract in a mouse model of intestinal colonization with pooled mutants (43).…”

Candida albicansdimorphism as a therapeutic target

“…The presence of a central venous catheter, parenteral nutrition, burns and gastrointestinal surgery list among the leading risk factors for disseminated candidiasis [11]. As C. albicans can grow as yeast in the gastrointestinal tract [20] or on the skin [21], these risk factors could certainly lead to hematogenous seeding with yeast cells. Biofilms on medical devices provide an alternative route; indeed, 'disperser' yeast cells can be produced from biofilms [22], which could readily seed the bloodstream.…”

“…As the expression of hyphalassociated genes was detected during asymptomatic carriage [23][24][25], it is possible that commensal cells grow in the hyphal form. However, this observation should be interpreted with caution, since hyphal-associated genes are expressed by yeast cells under certain conditions [19,20,26,27]. Indeed, Kumamoto et al have reported the expression of hyphal-associated genes by C. albicans colonizing the murine gastrointestinal tract (after removal of the bacterial flora), a niche where the dominant morphology was yeast cells [20,28].…”

The role of pattern recognition receptors in the innate recognition ofCandida albicans

“…1,6 C. albicans is a commensal fungus that colonize on gastrointestinal/genital mucosa of mammalians without causing disease in most healthy individuals, but in case the host defense is weakened under certain circumstances can C. albicans become pathogenic. [7][8][9][10] C. albicans may cause 2 types of infections: superficial infections (such as oral or vaginal candidiasis), and systemic infections (such as life-threatening bloodstream infections/candidaemia). 11 Polymorphological transition is the widely known virulence trait of C. albicans, 12 and the fungus can grow as whitephase yeast cells, GUT cells, opaque-phase cells, gray-phase cells, 13 chlamydospores, ture hyphae, and pseudohyphae.…”