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Protein Kinase A Regulates Autophagy-Associated Proteins Impacting Growth and Virulence of Aspergillus fumigatus.
Shwab, E Keats; Juvvadi, Praveen R; Shaheen, Shareef K; Allen, John; Waitt, Greg; Soderblom, Erik J; Asfaw, Yohannes G; Moseley, M Arthur; Steinbach, William J.
Afiliação
  • Shwab EK; Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA.
  • Juvvadi PR; Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA.
  • Shaheen SK; Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA.
  • Allen J; Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA.
  • Waitt G; Duke Proteomics Core Facility, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27701, USA.
  • Soderblom EJ; Duke Proteomics Core Facility, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27701, USA.
  • Asfaw YG; Department of Laboratory Animal Resources, Duke University Medical Center, Durham, NC 27710, USA.
  • Moseley MA; Duke Proteomics Core Facility, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27701, USA.
  • Steinbach WJ; Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA.
J Fungi (Basel) ; 8(4)2022 Mar 30.
Article em En | MEDLINE | ID: mdl-35448585
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.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article