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Hypoxia and extraintestinal dissemination of Candida albicans yeast forms
Adam S Kim1, Robb M Garni, Michelle J Henry-Stanley
1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Abstract:
Candida albicans is a pleomorphic fungus with budding yeast and filamentous forms, and is a frequent cause of complicating infections in patients who are postsurgical, in shock, and have trauma. Many cases of systemic candidiasis are thought to orginate from the intestine, but it is unclear if the filament or the yeast is the more invasive form. Because C. albicans is relatively noninvasive and because mesenteric ischemia is thought to facilitate extraintestinal microbial dissemination, wild-type C. albicans CAF2 and mutant HLC54 (defective in filament formation) were orally inoculated into antibiotic-treated mice that were housed exclusively in room air, or were intermittently exposed to 10% oxygen for 1-h intervals. Both strains of C. albicans colonized the cecum in similar numbers (approximately 10(6.7)/g). C. albicans translocation to the draining mesenteric lymph nodes was not detected in mice inoculated with CAF2 (normoxic or hypoxic) or in normoxic mice inoculated with HLC54, but was detected in 33% (P < 0.01) of hypoxic mice inoculated with HLC54. Using Caco-2 and HT-29 enterocytes cultivated on plastic dishes and pretreated for 48 h in 10% oxygen, adherence of C. albicans HLC54 was decreased compared with wild-type CAF2, and hypoxia had no noticeable effect on adherence of either CAF2 or HLC54. Using enterocytes cultivated on permeable 8-microm filters, transepithelial migration of C. albicans CAF2 and HLC54 appeared similar. Thus, C. albicans HLC54 (defective in filament formation) was more invasive in hypoxic mice compared with wild-type CAF2, and host factors (e.g., mesenteric ischemia) rather than an innate ability to interact with enterocytes might play a more important role in extraintestinal dissemination of C. albicans yeast forms.
Insights
The yeast form of Candida albicans, not the filament, was more invasive in hypoxic conditions. Host factors like mesenteric ischemia may be crucial for fungal dissemination.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Microbial Pathogenesis
Background:
- Candida albicans is a fungus causing infections, particularly in vulnerable patients.
- Systemic candidiasis often originates in the intestine, but the invasive form (yeast vs. filament) is debated.
- Mesenteric ischemia is suspected to promote microbial spread outside the gut.
Purpose of the Study:
- To investigate the invasiveness of Candida albicans yeast versus filament forms.
- To determine the role of hypoxia and host factors in Candida albicans dissemination.
- To compare the invasiveness of wild-type C. albicans with a filament-defective mutant.
Main Methods:
- Oral inoculation of wild-type (CAF2) and filament-defective (HLC54) C. albicans in mice under normoxic and hypoxic conditions.
- Assessing C. albicans colonization in the cecum and translocation to mesenteric lymph nodes.
- Evaluating fungal adherence to and transepithelial migration across enterocytes under varying oxygen levels.
Main Results:
- Both C. albicans strains colonized the cecum similarly.
- Translocation to lymph nodes was detected only in hypoxic mice infected with the filament-defective HLC54 strain.
- Hypoxia did not affect fungal adherence to enterocytes, and filament-defective mutants showed decreased adherence.
- Transepithelial migration was similar for both strains.
Conclusions:
- The yeast form of C. albicans, particularly a filament-defective mutant, demonstrated increased invasiveness in hypoxic environments.
- Host factors, such as mesenteric ischemia, may be more critical than the fungus's filament-forming ability for extraintestinal spread.
- The study suggests that C. albicans yeast forms are more invasive under specific host conditions.