Abstract:Candida glabrata has emerged as an important fungal pathogen of humans, causing life-threatening infections in immunocompromized patients. In contrast, mice do not develop disease upon systemic challenge, even with high infection doses. In this study we show that leucopenia, but not treatment with corticosteroids, leads to transiently increased fungal burdens in comparison to immunocompetent mice. However, even immunocompetent mice were not capable of clearing infections within four weeks. Tissue damage and immune responses to microabscesses were mild as monitored by clinical parameters, including blood enzyme levels, histology, myeloperoxidase and cytokines levels. Furthermore, we investigated the suitability of amino acid auxotrophic C. glabrata strains for in vitro and in vivo studies on fitness and or virulence. Histidine, leucine or tryptophan auxotrophy, as well as a combination of these auxotrophies, did not influence in vitro growth in rich medium. Survival of all auxotrophic strains in immunocompetent mice was similar to the parental wild type strain during the first week of infection and only mildly reduced four weeks after infection, suggesting that C. glabrata is capable of utilizing a broad range of host-derived nutrients during infection. These data suggest that C. glabrata histidine, leucine or tryptophan auxotrophic strains are suitable for generation of knockout mutants for in vivo studies. Notably, our work indicates that C. glabrata has successfully developed immune evasion strategies to survive, disseminate and persist within mammalian hosts.
Status: Published Type: Journal Article|Research Support, Non-u.s. Gov't PubMed ID: 20008535