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

ABSTRACT: Loss or inactivation of antivirulence genes is an adaptive strategy in pathogen evolution. Candida glabrata is an important opportunistic pathogen related to baker's yeast, with the ability to both quickly increase its intrinsic high level of azole resistance and persist within phagocytes. During C. glabrata's evolution as a pathogen, the mitochondrial DNA polymerase CgMip1 has been under positive selection. We show that CgMIP1 deletion not only triggers loss of mitochondrial function and a petite phenotype, but increases C. glabrata's azole and endoplasmic reticulum (ER) stress resistance and, importantly, its survival in phagocytes. The same phenotype is induced by fluconazole and by exposure to macrophages, conferring a cross-resistance between antifungals and immune cells

SUBMITTER: Siscar-Lewin S 

PROVIDER: S-EPMC8262853 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature