Autophagy in the Oral Pathogen Candida albicans

The opportunistic pathogen Candida albicans is responsible for a diverse range of oral disease. Over 90% of HIV/AIDS patients will suffer at least one episode of oropharyngeal candidiasis and usually these infections are recurrent. Immunocompetent denture wearers are also at significant risk of developing mucosal lesions caused by Candida species. Autophagic degradation of cytoplasmic material has been shown to be essential for starvation resistance, development and differentiation, and programmed cell death in higher eukaryotes. We have investigated the role of autophagy in C. albicans growth, differentiation and virulence. Objective: To determine the importance of autophagic degradation in the differentiation and virulence of a fungal pathogen. Methods: We cloned the C. albicans homologue of ATG9, a gene required for autophagy in Saccharomyces, and constructed a C. albicans gene deletion strain (atg9Δ). To confirm the mutant strain was blocked in autophagy we measured starvation resistance, autophagosome formation and trafficking of a fluorescent tagged cargo protein (Amino Peptidase I). Yeast-hypha differentiation was measured on M199 agar or in liquid FCS media. A mouse macrophage like cell line (J774A.1) was used as an in vitro model of Candida-macrophage interaction. Virulence was determined using a mouse model of disseminated infection. Results: As expected the atg9Δ mutant was blocked in autophagy. This rendered the mutant sensitive to nitrogen starvation. However, the mutant strain was unaffected in its capacity to undergo yeast-hypha differentiation and maintained ‘wild-type' levels of virulence during interaction with J774A.1 cells and in the mouse model of disseminated infection. Conclusion: Despite autophagy playing a major role in a diverse array of developmental and differentiation events in higher eukaryotes, autophagy was not required for C. albicans yeast-hypha differentiation, an event intimately linked with virulence of this organism. Furthermore, autophagy seems of little significance with respect to the virulence of C. albicans.

Supported by NCRR #P20RR020160.