Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis

Rivera-Lugo, Rafael; Deng, David; Anaya-Sanchez, Andrea; Tejedor-Sanz, Sara; Tang, Eugene; Reyes Ruiz, Valeria M.; Smith, Hans B.; Titov, Denis V.; Sauer, John-Demian; Skaar, Eric P.; Ajo-Franklin, Caroline M.; Portnoy, Daniel A.; Light, Samuel H.

doi:10.7554/eLife.75424

Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis

Journal Article · Tue Apr 05 00:00:00 EDT 2022 · eLife

DOI:https://doi.org/10.7554/eLife.75424· OSTI ID:1867302

; Deng, David; Anaya-Sanchez, Andrea; Tejedor-Sanz, Sara; Tang, Eugene; Reyes Ruiz, Valeria M.; Smith, Hans B.; ; ; Skaar, Eric P.; Ajo-Franklin, Caroline M.; Portnoy, Daniel A.;

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 >1000-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.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1867302

Alternate ID(s):: OSTI ID: 1867304
OSTI ID: 2469720

Journal Information:: eLife, Journal Name: eLife Vol. 11; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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