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Gastrointestinal colonization and systemic dissemination by Candida albicans and Candida tropicalis in intact and
L de Repentigny1, M Phaneuf, L G Mathieu
1Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, Quebec, Canada.
Abstract:
Gastrointestinal colonization and systemic dissemination by Candida albicans and Candida tropicalis were compared in intact and immunocompromised mice. Five-day-old CFW mice were inoculated by the oral-intragastric route with 1.0 x 10(7) CFU of two C. albicans and two C. tropicalis strains isolated from the blood of patients with acute leukemia and with C. albicans 4918 and its cerulenin-resistant mutant 4918-10. C. albicans and C. tropicalis spread to the lungs, liver, and kidneys within 30 min postinoculation, and organ CFU of the two species were comparable over the following 10 days. Close association of blastoconidia with the villous surface of the small intestine resulted in lysis of microvilli and then progressive invasion of villi. Blastoconidia within villi were surrounded by a conspicuous zone of clearing. Persistent colonization of the small and large intestines by C. albicans blood isolates and strains 4918 and 4918-10 was similar for 31 days after inoculation, but consistently exceeded that of C. tropicalis. In mice colonized with C. albicans, immunosuppression with cortisone acetate and cyclophosphamide on days 30 and 33 after inoculation increased stomach CFU 40- to 370-fold and intestinal CFU 30- to 80-fold. In contrast, persistent colonization by C. tropicalis was undetectable before immunosuppression and only became apparent after treatment. C. albicans disseminated more frequently and with higher organ CFU than C. tropicalis. Despite this fact, 20% of mice infected with C. tropicalis died, compared with 4% infected with C. albicans blood isolates. Indirect immunofluorescence revealed penetrative growth by Candida hyphae exclusively in the mucosa and submucosa of the stomach from immunosuppressed, persistently colonized mice. Taken together, the data indicate that C. tropicalis appears to be more virulent than C. albicans and that factors responsible for gastrointestinal colonization, systemic dissemination, and mortality in immunocompromised mice may not be identical.
Insights
Candida tropicalis shows higher virulence than Candida albicans in mice, causing more deaths despite less frequent dissemination. Immunocompromised states significantly increase Candida colonization and spread.
Area of Science:
- Mycology
- Infectious Diseases
- Immunology
Background:
- Candida species are opportunistic fungal pathogens.
- Gastrointestinal colonization is a precursor to systemic candidiasis.
- Understanding host-pathogen interactions is crucial for managing Candida infections.
Purpose of the Study:
- To compare gastrointestinal colonization and systemic dissemination of Candida albicans and Candida tropicalis in mice.
- To investigate the impact of immunosuppression on Candida infections.
- To assess the virulence and mortality associated with these Candida species.
Main Methods:
- Oral-intragastric inoculation of CFW mice with Candida albicans and Candida tropicalis strains.
- Monitoring of fungal load in organs (lungs, liver, kidneys) and intestines over time.
- Induction of immunosuppression using cortisone acetate and cyclophosphamide.
- Histological examination using indirect immunofluorescence.
Main Results:
- Both Candida species disseminated rapidly to organs within 30 minutes.
- Candida albicans showed persistent intestinal colonization, which was significantly enhanced by immunosuppression.
- Candida tropicalis colonization became apparent only after immunosuppression, yet it caused higher mortality.
- Hyphal growth was observed in the stomach mucosa and submucosa of immunosuppressed mice.
Conclusions:
- Candida tropicalis appears more virulent than Candida albicans in this mouse model.
- Factors governing gastrointestinal colonization, systemic spread, and mortality may differ between Candida species.
- Immunocompromised status dramatically increases susceptibility to Candida colonization and dissemination.