The NsrR regulon in nitrosative stress resistance of Salmonella enterica serovar Typhimurium

Joyce E. Karlinsey, Iel Soo Bang, Lynne A. Becker, Elaine R. Frawley, Steffen Porwollik, Hannah F. Robbins, Vinai Chittezham Thomas, Rodolfo Urbano, Michael Mcclelland, Ferric C. Fang

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42 Scopus citations

Abstract

Nitric oxide (NO·) is an important mediator of innate immunity. The facultative intracellular pathogen Salmonella has evolved mechanisms to detoxify and evade the antimicrobial actions of host-derived NO· produced during infection. Expression of the NO·-detoxifying flavohaemoglobin Hmp is controlled by the NO·-sensing transcriptional repressor NsrR and is required for Salmonella virulence. In this study we show that NsrR responds to very low NO· concentrations, suggesting that it plays a primary role in the nitrosative stress response. Additionally, we have defined the NsrR regulon in Salmonella enterica sv. Typhimurium 14028s using transcriptional microarray, qRT-PCR and in silico methods. A novel NsrR-regulated gene designated STM1808 has been identified, along with hmp, hcp-hcr, yeaR-yoaG, ygbA and ytfE. STM1808 and ygbA are important for S. Typhimurium growth during nitrosative stress, and the hcp-hcr locus plays a supportive role in NO· detoxification. ICP-MS analysis of purified STM1808 suggests that it is a zinc metalloprotein, with histidine residues H32 and H82 required for NO· resistance and zinc binding. Moreover, STM1808 and ytfE promote Salmonella growth during systemic infection of mice. Collectively, these findings demonstrate that NsrR-regulated genes in addition to hmp are important for NO· detoxification, nitrosative stress resistance and Salmonella virulence.

Original languageEnglish (US)
Pages (from-to)1179-1193
Number of pages15
JournalMolecular Microbiology
Volume85
Issue number6
DOIs
StatePublished - Sep 2012

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Karlinsey, J. E., Bang, I. S., Becker, L. A., Frawley, E. R., Porwollik, S., Robbins, H. F., Thomas, V. C., Urbano, R., Mcclelland, M., & Fang, F. C. (2012). The NsrR regulon in nitrosative stress resistance of Salmonella enterica serovar Typhimurium. Molecular Microbiology, 85(6), 1179-1193. https://doi.org/10.1111/j.1365-2958.2012.08167.x