Next Article in Journal
Heterologous Expression of Secondary Metabolite Genes in Trichoderma reesei for Waste Valorization
Next Article in Special Issue
Taking a Closer Look: Clinical and Histopathological Characteristics of Culture-Positive versus Culture-Negative Pulmonary Mucormycosis
Previous Article in Journal
Industrial-Scale Production of Mycotoxin Binder from the Red Yeast Sporidiobolus pararoseus KM281507
Previous Article in Special Issue
Targeted Delivery of Antifungal Liposomes to Rhizopus delemar
 
 
Article

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

1
Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA
2
Duke Proteomics Core Facility, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27701, USA
3
Department of Laboratory Animal Resources, Duke University Medical Center, Durham, NC 27710, USA
4
Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USA
*
Author to whom correspondence should be addressed.
Current Address: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Academic Editor: Jatin Mahesh Vyas
J. Fungi 2022, 8(4), 354; https://doi.org/10.3390/jof8040354
Received: 28 February 2022 / Revised: 14 March 2022 / Accepted: 28 March 2022 / Published: 30 March 2022
(This article belongs to the Special Issue Advances Against Aspergillosis and Mucormycosis 2022)
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. View Full-Text
Keywords: Aspergillus; aspergillosis; protein kinase A; autophagy; nutrient sensing; phosphorylation; pathogenesis; cell wall; filamentous fungi; proteomics Aspergillus; aspergillosis; protein kinase A; autophagy; nutrient sensing; phosphorylation; pathogenesis; cell wall; filamentous fungi; proteomics
Show Figures

Figure 1

MDPI and ACS Style

Shwab, E.K.; Juvvadi, P.R.; Shaheen, S.K.; Allen, J., IV; Waitt, G.; Soderblom, E.J.; Asfaw, Y.G.; Moseley, M.A.; Steinbach, W.J. Protein Kinase A Regulates Autophagy-Associated Proteins Impacting Growth and Virulence of Aspergillus fumigatus. J. Fungi 2022, 8, 354. https://doi.org/10.3390/jof8040354

AMA Style

Shwab EK, Juvvadi PR, Shaheen SK, Allen J IV, Waitt G, Soderblom EJ, Asfaw YG, Moseley MA, Steinbach WJ. Protein Kinase A Regulates Autophagy-Associated Proteins Impacting Growth and Virulence of Aspergillus fumigatus. Journal of Fungi. 2022; 8(4):354. https://doi.org/10.3390/jof8040354

Chicago/Turabian Style

Shwab, E. Keats, Praveen R. Juvvadi, Shareef K. Shaheen, John Allen IV, Greg Waitt, Erik J. Soderblom, Yohannes G. Asfaw, M. Arthur Moseley, and William J. Steinbach. 2022. "Protein Kinase A Regulates Autophagy-Associated Proteins Impacting Growth and Virulence of Aspergillus fumigatus" Journal of Fungi 8, no. 4: 354. https://doi.org/10.3390/jof8040354

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop