Master Sculptor at Work: Enteropathogenic Escherichia coli Infection Uniquely Modifies Mitochondrial Proteolysis during Its Control of Human Cell Death

Author:

Marshall Natalie C.12ORCID,Thejoe Maichael2ORCID,Klein Theo3ORCID,Serapio-Palacios Antonio2ORCID,Santos Andrew S.12ORCID,von Krosigk Niklas2ORCID,Kizhakkedathu Jayachandran N.4ORCID,Stoynov Nikolay2,Foster Leonard J.25ORCID,Overall Christopher M.35ORCID,Finlay B. Brett125ORCID

Affiliation:

1. Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada

2. Michael Smith Laboratories, University of British Columbia, Vancouver, Canada

3. Life Sciences Institute and Department of Oral Biological & Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, Canada

4. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

5. Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, Canada

Abstract

To our knowledge, this is the first study of the mitochondrial proteome or N-terminome during bacterial infection. Identified cleavage sites that had not been previously reported in the mitochondrial N-terminome and that were not generated in canonical apoptosis revealed a pathogen-specific strategy to control human cell apoptosis. These data inform new mechanisms of virulence factors targeting mitochondria and apoptosis during infection and highlight how enteropathogenic Escherichia coli (EPEC) manipulates human cell death pathways during infection, including candidate substrates of an EPEC protease within mitochondria. This understanding informs the development of new antivirulence strategies against the many human pathogens that target mitochondria during infection. Therefore, m itochondrial s table isotope labeling by amino acids in cell culture- t erminal a mine i sotopic l abeling of s ubstrates (MS-TAILS) is useful for studying other pathogens targeting human cell compartments.

Funder

Michael Smith Foundation for Health Research

Canada Research Chairs

Gouvernement du Canada | Canadian Institutes of Health Research

Canada Foundation for Innovation

Genome Canada

Ministry of Technology, Innovation and Citizens' Services | British Columbia Knowledge Development Fund

Publisher

American Society for Microbiology

Subject

Computer Science Applications,Genetics,Molecular Biology,Modelling and Simulation,Ecology, Evolution, Behavior and Systematics,Biochemistry,Physiology,Microbiology

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