Transient Mitochondria Dysfunction Confers Fungal Cross-Resistance against Phagocytic Killing and Fluconazole.

摘要: Loss or inactivation of antivirulence genes is an adaptive strategy in pathogen evolution. Candida glabrata important opportunistic related to baker's yeast, with the ability both quickly increase its intrinsic high level azole resistance and persist within phagocytes. During C. glabrata's evolution as a pathogen, mitochondrial DNA polymerase CgMip1 has been under positive selection. We show that CgMIP1 deletion not only triggers loss function petite phenotype, but increases endoplasmic reticulum (ER) stress and, importantly, survival The same phenotype induced by fluconazole exposure macrophages, conferring cross-resistance between antifungals immune cells, can be found clinical isolates despite slow growth strains. This suggests constitutes bet-hedging potentially, relevant cause resistance. Mitochondrial may therefore considered potential factor. IMPORTANCE whose incidence increasing last 40 years. It risen become most prominent non-Candida albicans (NCAC) species candidemia, constituting about one-third United States, steadily European countries Australia. Despite importance, pathogenicity strategies remain poorly understood. Our research shows resulting advantageous for cope infection-related stressors, such host defenses. (cross-)resistance against these factors have major implications outcome infections this fungal pathogen.