Nitrite Derived from Endogenous Bacterial Nitric Oxide Synthase Activity Promotes Aerobic Respiration.

Sujata S Chaudhari,Matthew C Zimmerman,Paul D Fey,Minji Kim,Robert Powers,Elizabeth H Hutfless,Shulei Lei,Abdulelah A Alqarzaee,Fareha Razvi,Vinai C Thomas,Andreas Peschel,Michael S Gilmore

doi:10.1128/mbio.00887-17

Abstract

ABSTRACTMacrophage-derived nitric oxide (NO·) is a crucial effector against invading pathogens. Yet, paradoxically, several bacterial species, including some pathogens, are known to endogenously produce NO· via nitric oxide synthase (NOS) activity, despite its apparent cytotoxicity. Here, we reveal a conserved role for bacterial NOS in activating aerobic respiration. We demonstrate that nitrite generated from endogenous NO· decomposition stimulates quinol oxidase activity in Staphylococcus aureus and increases the rate of cellular respiration. This not only supports optimal growth of this organism but also prevents a dysbalance in central metabolism. Further, we also show that activity of the SrrAB two-component system alleviates the physiological defects of the nos mutant. Our findings suggest that NOS and SrrAB constitute two distinct but functionally redundant routes for controlling staphylococcal respiration during aerobic growth.

Highlights

Macrophage-derived nitric oxide (NO·) is a crucial effector against invading pathogens
The predominant community-associated methicillin-resistant S. aureus (CA-MRSA) isolates of the USA300 lineage have acquired an additional copy of the arginine deiminase (ADI) pathway in the arginine catabolic mobile element (ACME), a genetic determinant that has been linked to its overwhelming success as a pathogen [3]
This is not entirely surprising, since arginine transport into cells is inhibited by the presence of excess glucose during exponential growth, it does suggest a potential role for nitric oxide synthase (NOS) in post-exponential-phase metabolism

Summary

Introduction

Macrophage-derived nitric oxide (NO·) is a crucial effector against invading pathogens. IMPORTANCE Despite its potential autotoxic effects, several bacterial species, including pathogenic staphylococcal species, produce NO· endogenously through nitric oxide synthase (NOS) activity. Various heme-based NO· sensor domain (H-NOX)-containing proteins such as eukaryotic sGC are present in bacterial species and can control c-di-GMP levels to modulate various physiologic processes [9] Despite these broad similarities, reports that suggest whether NO· itself can act as a signaling molecule in bacteria are scarce [9]. Reports that suggest whether NO· itself can act as a signaling molecule in bacteria are scarce [9] In addition to these proposed functions, NO· is rapidly converted to more stable metabolites such as nitrite and nitrate under aerobic conditions and a role for these metabolites in NO·-dependent processes has not been rigorously pursued

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