Self-regulation of Candida albicans population size during GI colonization.
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.
White
Sarah Jane
SJ
Department of Molecular Biology and Microbiology, Tufts University, Boston, Massachusetts, United States of America.
Rosenbach
Ari
A
Lephart
Paul
P
Nguyen
Diem
D
Benjamin
Alana
A
Tzipori
Saul
S
Whiteway
Malcolm
M
Mecsas
Joan
J
Kumamoto
Carol A
CA
D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000472:pathogenicity*; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology*; D002432:Cecum / Q000382:microbiology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005656:Fungal Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal; D005856:Germ-Free Life; D054884:Host-Pathogen Interactions / Q000502:physiology*; D007082:Ileum / Q000382:microbiology* / Q000473:pathology; D007165:Immunosuppression Therapy; D051379:Mice; D046228:Microarray Analysis; D011157:Population Dynamics; D012333:RNA, Messenger / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013552:Swine; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D012333:RNA, Messenger; D014157:Transcription Factors