NO-mediated cytoprotection: Instant adaptation to oxidative stress in bacteria

doi:10.1073/pnas.0504307102

NO-mediated cytoprotection: Instant adaptation to oxidative stress in bacteria

Ivan Gusarov and
Evgeny Nudler*

Department of Biochemistry, New York University Medical Center, New York, NY 10016

Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved July 29, 2005 (received for review May 25, 2005)

Abstract

Numerous sophisticated systems have been described that protect bacteria from increased levels of reactive oxygen species. Although indispensable during prolonged oxidative stress, these response systems depend on newly synthesized proteins, and are hence both time and energy consuming. Here, we describe an “express” cytoprotective system in Bacillus subtilis which depends on nitric oxide (NO). We show that NO immediately protects bacterial cells from reactive oxygen species by two independent mechanisms. NO transiently suppresses the enzymatic reduction of free cysteine that fuels the damaging Fenton reaction. In addition, NO directly reactivates catalase, a major antioxidant enzyme that has been inhibited in vivo by endogenous cysteine. Our data also reveal a critical role for bacterial NO-synthase in adaptation to oxidative stress associated with fast metabolic changes, and suggest a possible role for NO in defending pathogens against immune oxidative attack.

Footnotes

↵ * To whom correspondence should be addressed. E-mail: evgeny.nudler{at}med.nyu.edu.
Author contributions: E.N. designed research; I.G. performed research; I.G. and E.N. analyzed data; and E.N. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: Cm, chloramphenicol; mBB, monobromobimane; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium inner salt; NOS, NO synthase; RE, reducing equivalents; TepAu, chloro(triethylphosphine)gold(I); Trx, thioredoxin; TrxRed, Trx reductase.