Conserved Autophagy Pathway Contributes to Stress Tolerance and Virulence and Differentially Controls Autophagic Flux Upon Nutrient Starvation in Cryptococcus neoformans.

摘要: Autophagy is mainly a catabolic process, which used to cope with nutrient deficiency and various stress conditions. Human environment often imposes stresses on Cryptococcus neoformans, major fungal pathogen of immunocompromised individuals; therefore, autophagic response C. neoformans these determines its survival in the host. However, systematic study how autophagy related (ATG) genes influence flux, virulence, pathogenicity lacking. In this study, 22 ATG-deficient strains were constructed investigate their roles pathogenesis, response, starvation tolerance flux neoformans. Our results showed that Atg6 Atg14-03 significantly affect growth at 37°C laccase production. Additionally, atg2Δ atg6Δ sensitive oxidative caused by hydrogen peroxide. Approximately half atgΔ displayed higher sensitivity 1.5 M NaCl remarkably lower virulence Galleria mellonella model than wild type. Autophagic was dependent Atg1-Atg13, Atg5-Atg12-Atg16, Atg2-Atg18 complexes Atg11. Cleavage green fluorescent protein (GFP) from Atg8 difficult detect defective mutants; however, it detected atg3Δ, atg4Δ, atg14Δ strains. no homologs Saccharomyces cerevisiae ATG10 indicate ATG contribute differentially carbon nitrogen compared S. cerevisiae. Overall, advances our knowledge specific