Protein Kinase A Regulates Autophagy-Associated Proteins Impacting Growth and Virulence of Aspergillus fumigatus.

Journal Article (Journal Article)

Cellular recycling via autophagy-associated proteins is a key catabolic pathway critical to invasive fungal pathogen growth and virulence in the nutrient-limited host environment. Protein kinase A (PKA) is vital for the growth and virulence of numerous fungal pathogens. However, the underlying basis for its regulation of pathogenesis remains poorly understood in any species. Our Aspergillus fumigatus PKA-dependent whole proteome and phosphoproteome studies employing advanced mass spectroscopic approaches identified numerous previously undefined PKA-regulated proteins in catabolic pathways. Here, we demonstrate reciprocal inhibition of autophagy and PKA activity, and identify 16 autophagy-associated proteins as likely novel PKA-regulated effectors. We characterize the novel PKA-phosphoregulated sorting nexin Atg20, and demonstrate its importance for growth, cell wall stress response, and virulence of A. fumigatus in a murine infection model. Additionally, we identify physical and functional interaction of Atg20 with previously characterized sorting nexin Atg24. Furthermore, we demonstrate the importance of additional uncharacterized PKA-regulated putative autophagy-associated proteins to hyphal growth. Our data presented here indicate that PKA regulates the autophagy pathway much more extensively than previously known, including targeting of novel effector proteins with fungal-specific functions important for invasive disease.

Full Text

Duke Authors

Cited Authors

  • Shwab, EK; Juvvadi, PR; Shaheen, SK; Allen, J; Waitt, G; Soderblom, EJ; Asfaw, YG; Moseley, MA; Steinbach, WJ

Published Date

  • March 30, 2022

Published In

Volume / Issue

  • 8 / 4

PubMed ID

  • 35448585

Pubmed Central ID

  • PMC9029100

Electronic International Standard Serial Number (EISSN)

  • 2309-608X

Digital Object Identifier (DOI)

  • 10.3390/jof8040354

Language

  • eng

Conference Location

  • Switzerland