Functional Coupling between the Unfolded Protein Response and Endoplasmic Reticulum/Golgi Ca 2+ -ATPases Promotes Stress Tolerance, Cell Wall Biosynthesis, and Virulence of Aspergillus fumigatus

Author:

Weichert Martin1,Guirao-Abad José1,Aimanianda Vishukumar2ORCID,Krishnan Karthik1,Grisham Christina1,Snyder Patrick1,Sheehan Alex1,Abbu Ruthvik R.1,Liu Hong3,Filler Scott G.3ORCID,Gruenstein Eric I.4,Latgé Jean-Paul5,Askew David S.1

Affiliation:

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

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

3. Division of Infectious Diseases, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA

4. Department of Molecular Genetics, Biochemistry & Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

5. Unité des Aspergillus, Institut Pasteur, Paris, France

Abstract

The UPR is an intracellular signal transduction pathway that maintains homeostasis of the ER. The pathway is also tightly linked to the expression of virulence-related traits in diverse species of human-pathogenic and plant-pathogenic fungal species, including the predominant mold pathogen infecting humans, Aspergillus fumigatus . Despite advances in the understanding of UPR signaling, the linkages and networks that are governed by this pathway are not well defined. In this study, we revealed that the UPR is a major driving force for stimulating Ca 2+ influx at the ER and Golgi membranes and that the coupling between the UPR and Ca 2+ import is important for virulence, cell wall biosynthesis, and resistance to antifungal compounds that inhibit Ca 2+ signaling.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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