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The transcriptional regulator VarN contributes to Salmonella Typhimurium growth in macrophages and virulence in mice.
Res Microbiol. 2018 May - Jun; 169(4-5):214-221.RM

Abstract

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major intracellular pathogen of humans and animals and its survival and growth in macrophages is essential for its pathogenicity. The S. Typhimurium genome encodes more than 50 putative regulatory proteins, but their involvement in pathogenicity and their regulatory roles are largely unknown. In this study, we investigated the biological function of the S. Typhimurium STM4320 gene (named varN), which encodes a putative MerR family transcriptional regulator. We found that varN is upregulated 2.6- to 6.8-fold after S. Typhimurium enters murine macrophages. A varN mutant reduced S. Typhimurium growth in murine macrophages and attenuated virulence in mice. Moreover, we showed that deletion of varN decreased the transcription of Salmonella pathogenicity island-2 (SPI-2) genes, which are required for S. Typhimurium growth in macrophages, indicative of the positive regulation of SPI-2 by VarN. We confirmed that the virulence defects of the varN mutant are entirely dependent on its regulation of SPI-2. Thus, our results revealed that VarN is a novel activator of the expression of SPI-2 genes and contributes to S. Typhimurium growth in macrophages and virulence in mice. Our findings provide a significant example of how a putative regulatory protein facilitates S. Typhimurium pathogenicity.

Authors+Show Affiliations

TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, China. Electronic address: 2120150187@mail.nankai.edu.cn.TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, China. Electronic address: lxmxiaomin0316@163.com.Tianjin Institute of Pharmaceutical Research New Drug Evaluation Co.Ltd, Binhai New Area, Tianjin 300301, China. Electronic address: sunshuangyong@163.com.TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin 300457, China. Electronic address: jianglingyan@nankai.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29751061

Citation

Jiang, Xiaohan, et al. "The Transcriptional Regulator VarN Contributes to Salmonella Typhimurium Growth in Macrophages and Virulence in Mice." Research in Microbiology, vol. 169, no. 4-5, 2018, pp. 214-221.
Jiang X, Li X, Sun S, et al. The transcriptional regulator VarN contributes to Salmonella Typhimurium growth in macrophages and virulence in mice. Res Microbiol. 2018;169(4-5):214-221.
Jiang, X., Li, X., Sun, S., & Jiang, L. (2018). The transcriptional regulator VarN contributes to Salmonella Typhimurium growth in macrophages and virulence in mice. Research in Microbiology, 169(4-5), 214-221. https://doi.org/10.1016/j.resmic.2018.03.003
Jiang X, et al. The Transcriptional Regulator VarN Contributes to Salmonella Typhimurium Growth in Macrophages and Virulence in Mice. Res Microbiol. 2018 May - Jun;169(4-5):214-221. PubMed PMID: 29751061.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The transcriptional regulator VarN contributes to Salmonella Typhimurium growth in macrophages and virulence in mice. AU - Jiang,Xiaohan, AU - Li,Xiaomin, AU - Sun,Shuangyong, AU - Jiang,Lingyan, Y1 - 2018/05/08/ PY - 2018/01/11/received PY - 2018/03/21/revised PY - 2018/03/29/accepted PY - 2018/5/12/pubmed PY - 2018/10/12/medline PY - 2018/5/12/entrez KW - Growth in macrophages KW - Regulatory protein KW - SPI-2 gene expression KW - Salmonella Typhimurium KW - VarN KW - Virulence SP - 214 EP - 221 JF - Research in microbiology JO - Res Microbiol VL - 169 IS - 4-5 N2 - Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major intracellular pathogen of humans and animals and its survival and growth in macrophages is essential for its pathogenicity. The S. Typhimurium genome encodes more than 50 putative regulatory proteins, but their involvement in pathogenicity and their regulatory roles are largely unknown. In this study, we investigated the biological function of the S. Typhimurium STM4320 gene (named varN), which encodes a putative MerR family transcriptional regulator. We found that varN is upregulated 2.6- to 6.8-fold after S. Typhimurium enters murine macrophages. A varN mutant reduced S. Typhimurium growth in murine macrophages and attenuated virulence in mice. Moreover, we showed that deletion of varN decreased the transcription of Salmonella pathogenicity island-2 (SPI-2) genes, which are required for S. Typhimurium growth in macrophages, indicative of the positive regulation of SPI-2 by VarN. We confirmed that the virulence defects of the varN mutant are entirely dependent on its regulation of SPI-2. Thus, our results revealed that VarN is a novel activator of the expression of SPI-2 genes and contributes to S. Typhimurium growth in macrophages and virulence in mice. Our findings provide a significant example of how a putative regulatory protein facilitates S. Typhimurium pathogenicity. SN - 1769-7123 UR - https://www.unboundmedicine.com/medline/citation/29751061/The_transcriptional_regulator_VarN_contributes_to_Salmonella_Typhimurium_growth_in_macrophages_and_virulence_in_mice_ DB - PRIME DP - Unbound Medicine ER -