Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis

作者：Rafael Rivera‐Lugo, David Y.B. Deng, Andrea Anaya-Sanchez, Sara Tejedor‐Sanz, Eugene Tang, Reyes Ruiz, Valeria M., Hans B. Smith, Denis V. Titov, John‐Demian Sauer, Eric Patrick Skaar, Caroline Marie Ajo-Franklin, Daniel A. Portnoy, Samuel H. Light · 发表于：University of Chicago · 年份：2022 · DOI：10.6082/xrgq5-r4x92 · 被引用次数：24 · 研究领域：Advanced Nanomaterials in Catalysis、Listeria monocytogenes in Food Safety、Endoplasmic Reticulum Stress and Disease

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.