Pleiotropic Effects of the P5-Type ATPase SpfA on Stress Response Networks Contribute to Virulence in the Pathogenic Mold Aspergillus fumigatus

Author:

Guirao-Abad José P.1,Weichert Martin1ORCID,Luengo-Gil Ginés2,Sze Wah Wong Sarah3,Aimanianda Vishukumar3ORCID,Grisham Christina1,Malev Nikita1,Reddy Shivani1,Woollett Laura1,Askew David S.1ORCID

Affiliation:

1. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

2. Clinical Analysis and Pathology Department, Group of Molecular Pathology and Pharmacogenetics, Instituto Murciano de Investigación Biosanitaria (IMIB), Hospital Universitario Santa Lucía, Cartagena, Spain

3. Institut Pasteur, Molecular Mycology Unit, CNRS, UMR2000, Paris, France

Abstract

The fungal UPR is an adaptive signaling pathway in the ER that buffers fluctuations in ER stress but also serves as a virulence regulatory hub in species of pathogenic fungi that rely on secretory pathway homeostasis for pathogenicity. This study demonstrates that the gene encoding the ER-localized P5-type ATPase SpfA is a downstream target of the UPR in the pathogenic mold A. fumigatus and that it works together with a second ER-localized P-type ATPase, SrcA, to support ER homeostasis, oxidative stress resistance, susceptibility to antifungal drugs, and virulence of A. fumigatus .

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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