Published April 5, 2022
| Version v1
Journal article
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Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis
Creators
- 1. University of California, Berkeley
- 2. Rice University
- 3. Vanderbilt University
- 4. University of Wisconsin-Madison
- 5. University of Chicago
Description
Cellular respiration is essential for multiple bacterial pathogens and a validated antibiotic target. In addition to driving oxidative phosphorylation, bacterial respiration has a variety of ancillary functions that obscure its contribution to pathogenesis. We find here that the intracellular pathogen Listeria monocytogenes encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis. Loss of respiration decreased NAD+ regeneration, but this could be specifically reversed by heterologous expression of a water-forming NADH oxidase (NOX). NOX expression fully rescued intracellular growth defects and increased L. monocytogenes loads >1,000- fold in a mouse infection model. Consistent with NAD+ regeneration maintaining L. monocytogenes viability and enabling immune evasion, a respiration-deficient strain exhibited elevated bacteriolysis within the host cytosol and NOX expression rescued this phenotype. These studies show that NAD+ regeneration represents a major role of L. monocytogenes respiration and highlight the nuanced relationship between bacterial metabolism, physiology, and pathogenesis.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.Files
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Additional details
Identifiers
- DOI
- 10.7554/eLife.75424
- Other
- oai:uchicago.tind.io:9874
Related works
- Cites
- https://doi.org/10.1101/2021.11.25.470024 (URL)
Funding
- National Institutes of Health
- T32GM007215
- National Institutes of Health
- R01AI137070
- National Institutes of Health
- R01AI073843
- National Institutes of Health
- 1P01AI063302
- National Institutes of Health
- 1R01AI27655
- National Institutes of Health
- K22AI144031
- National Academies of Sciences, Engineering, and Medicine
- Ford Foundation Fellowship
- University of California
- Dissertation-Year Fellowship
- Kinship Foundation
- Searle Scholars Program
- Howard Hughes Medical Institute
- Hanna H. Gray Fellows Program
- Burroughs Wellcome Fund
- Postdoctoral Enrichment Program
- Vanderbilt University
- Academic Pathways Postdoctoral Fellowship
- Department of Energy
- DE-AC02-05CH11231