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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\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis. Loss of respiration decreased NAD\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    loads &gt;1000-fold in a mouse infection model. Consistent with NAD\n                    <jats:sup>+<\/jats:sup>\n                    regeneration maintaining\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    regeneration represents a major role of\n                    <jats:italic>L. monocytogenes<\/jats:italic>\n                    respiration and highlight the nuanced relationship between bacterial metabolism, physiology, and pathogenesis.\n                  <\/jats:p>","DOI":"10.7554\/elife.75424","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T08:04:08Z","timestamp":1649145848000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.75424","source":"Crossref","is-referenced-by-count":34,"title":["Listeria monocytogenes requires cellular respiration for NAD+ regeneration and 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