ATG Genes Influence the Virulence of Cryptococcus neoformans through Contributions beyond Core Autophagy Functions [Fungal and Parasitic Infections]

In this study, we showed that deletion of each of the ATG1, ATG7, ATG8, and ATG9 genes in C. neoformans leads to autophagy-related phenotypes, including impaired amino acid homeostasis under nitrogen starvation. In addition, the atg mutants were hypersensitive to inhibition of the ubiquitin-proteasome system, a finding consistent with a role in amino acid homeostasis. Although each atg mutant was not markedly impaired in virulence factor production in vitro, we found that all four ATG genes contribute to C. neoformans virulence in a murine inhalation model of cryptococcosis. Interestingly, these mutants displayed significant differences in their ability to promote disease development. A more detailed investigation of virulence for the atg1 and atg8 mutants revealed that both strains stimulated an exaggerated host immune response, which, in turn, contributed to disease severity. Overall, our results suggest that different ATG genes are involved in nonautophagic functions and contribute to C. neoformans virulence beyond their core functions in autophagy.

Source: Infection and Immunity - August 22, 2018 Category: Infectious Diseases Authors: Ding, H., Caza, M., Dong, Y., Arif, A. A., Horianopoulos, L. C., Hu, G., Johnson, P., Kronstad, J. W. Tags: Fungal and Parasitic Infections Source Type: research