{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:43:06Z","timestamp":1790804586664,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R21AI132911-02"],"award-info":[{"award-number":["5R21AI132911-02"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/jof8040354","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:28:39Z","timestamp":1648675719000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Protein Kinase A Regulates Autophagy-Associated Proteins Impacting Growth and Virulence of Aspergillus fumigatus"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8383-1031","authenticated-orcid":false,"given":"E. Keats","family":"Shwab","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen R.","family":"Juvvadi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shareef K.","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"John","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Waitt","sequence":"additional","affiliation":[{"name":"Duke Proteomics Core Facility, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik J.","family":"Soderblom","sequence":"additional","affiliation":[{"name":"Duke Proteomics Core Facility, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohannes G.","family":"Asfaw","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Resources, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arthur","family":"Moseley","sequence":"additional","affiliation":[{"name":"Duke Proteomics Core Facility, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Steinbach","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA"},{"name":"Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.1128\/IAI.00565-06","article-title":"Deletion of the regulatory subunit of protein kinase A in Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and virulence","volume":"74","author":"Zhao","year":"2006","journal-title":"Infect. 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