A URA3 null mutant of Candida albicans (CAI-4) causes oro-oesophageal and gastric candidiasis and is lethal for gnotobiotic, transgenic mice (Tgepsilon26) that are deficient in both natural killer and T cells.
Current data suggest that functional URA3 genes are necessary for the full pathogenesis of Candida albicans. Herein it is shown that a putatively avirulent URA3/URA3 null mutant of C. albicans (CAI-4) can colonize the murine alimentary tract, invade oro-oesophageal and gastric tissues with yeasts and hyphae, evoke a granulocyte-dominated inflammatory response, and kill transgenic mice that are deficient for both natural killer cells and T cells. Because C. albicans-colonized (gnotobiotic) mice lack a viable prokaryotic microbiota, this study also demonstrates that the gut microbiome is not required to supply the mutant's nutritional needs. The gnotobiotic murine model described herein can be used to assess the capacity of C. albicans mutants to colonize and infect cutaneous, mucosal and systemic tissues and kill the susceptible host via a clinically common, natural route of infection; namely the alimentary tract.
Balish
Edward
E
Departments of Microbiology and Immunology, and Stomatology, Medical University of South Carolina, Charleston, SC 29403, USA.
D000818:Animals; D002176:Candida albicans / Q000235:genetics* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology* / Q000401:mortality; D002180:Candidiasis, Oral / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D002432:Cecum / Q000382:microbiology; D004935:Esophageal Diseases / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D004947:Esophagus / Q000382:microbiology; D005656:Fungal Proteins / Q000235:genetics*; D005856:Germ-Free Life; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D017384:Sequence Deletion; D013270:Stomach / Q000382:microbiology; D013272:Stomach Diseases / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D013601:T-Lymphocytes / Q000276:immunology; D014059:Tongue / Q000382:microbiology
D005656:Fungal Proteins