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Contribution of the Cpx envelope stress system to metabolism and virulence regulation in Salmonella enterica serovar Typhimurium.
PLoS One. 2019; 14(2):e0211584.Plos

Abstract

The Cpx-envelope stress system regulates the expression of virulence factors in many Gram-negative pathogens. In Salmonella enterica serovar Typhimurium deletion of the sensor kinase CpxA but not of the response regulator CpxR results in the down regulation of the key regulator for invasion, HilA encoded by the Salmonella pathogenicity island 1 (SPI-1). Here, we provide evidence that cpxA deletion interferes with dephosphorylation of CpxR resulting in increased levels of active CpxR and consequently in misregulation of target genes. 14 potential operons were identified to be under direct control of CpxR. These include the virulence determinants ecotin, the omptin PgtE, and the SPI-2 regulator SsrB. The Tat-system and the PocR regulator that together promote anaerobic respiration of tetrathionate on 1,2-propanediol are also under direct CpxR control. Notably, 1,2-propanediol represses hilA expression. Thus, our work demonstrates for the first time the involvement of the Cpx system in a complex network mediating metabolism and virulence function.

Authors+Show Affiliations

Department of Microbial Physiology, Humboldt Universität zu Berlin, Berlin, Germany.Department of Microbial Physiology, Humboldt Universität zu Berlin, Berlin, Germany.Department of Microbial Physiology, Humboldt Universität zu Berlin, Berlin, Germany.Genomic Core Facility, Max-Planck-Institute for Infection Biology, Berlin, Germany.Department of Molecular Biology, Max-Planck-Institute for Infection Biology, Berlin, Germany.Department of Infection Biology, Helmholtz Center for Infection Research, Braunschweig, Germany.Department of Infection Biology, Helmholtz Center for Infection Research, Braunschweig, Germany.Department of Microbiology, Humboldt Universität zu Berlin, Berlin, Germany.Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany.Department of Microbiology and Molecular Genetics, University of California, Irvine, California, United States of America.Department of Microbiology and Molecular Genetics, University of California, Irvine, California, United States of America.Department of Molecular Biology, Max-Planck-Institute for Infection Biology, Berlin, Germany.Department of Microbial Physiology, Humboldt Universität zu Berlin, Berlin, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30716090

Citation

Subramaniam, Sivaraman, et al. "Contribution of the Cpx Envelope Stress System to Metabolism and Virulence Regulation in Salmonella Enterica Serovar Typhimurium." PloS One, vol. 14, no. 2, 2019, pp. e0211584.
Subramaniam S, Müller VS, Hering NA, et al. Contribution of the Cpx envelope stress system to metabolism and virulence regulation in Salmonella enterica serovar Typhimurium. PLoS One. 2019;14(2):e0211584.
Subramaniam, S., Müller, V. S., Hering, N. A., Mollenkopf, H., Becker, D., Heroven, A. K., Dersch, P., Pohlmann, A., Tedin, K., Porwollik, S., McClelland, M., Meyer, T. F., & Hunke, S. (2019). Contribution of the Cpx envelope stress system to metabolism and virulence regulation in Salmonella enterica serovar Typhimurium. PloS One, 14(2), e0211584. https://doi.org/10.1371/journal.pone.0211584
Subramaniam S, et al. Contribution of the Cpx Envelope Stress System to Metabolism and Virulence Regulation in Salmonella Enterica Serovar Typhimurium. PLoS One. 2019;14(2):e0211584. PubMed PMID: 30716090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contribution of the Cpx envelope stress system to metabolism and virulence regulation in Salmonella enterica serovar Typhimurium. AU - Subramaniam,Sivaraman, AU - Müller,Volker S, AU - Hering,Nina A, AU - Mollenkopf,Hans, AU - Becker,Daniel, AU - Heroven,Ann Kathrin, AU - Dersch,Petra, AU - Pohlmann,Anne, AU - Tedin,Karsten, AU - Porwollik,Steffen, AU - McClelland,Michael, AU - Meyer,Thomas F, AU - Hunke,Sabine, Y1 - 2019/02/04/ PY - 2018/10/17/received PY - 2019/01/16/accepted PY - 2019/2/5/entrez PY - 2019/2/5/pubmed PY - 2019/11/2/medline SP - e0211584 EP - e0211584 JF - PloS one JO - PLoS One VL - 14 IS - 2 N2 - The Cpx-envelope stress system regulates the expression of virulence factors in many Gram-negative pathogens. In Salmonella enterica serovar Typhimurium deletion of the sensor kinase CpxA but not of the response regulator CpxR results in the down regulation of the key regulator for invasion, HilA encoded by the Salmonella pathogenicity island 1 (SPI-1). Here, we provide evidence that cpxA deletion interferes with dephosphorylation of CpxR resulting in increased levels of active CpxR and consequently in misregulation of target genes. 14 potential operons were identified to be under direct control of CpxR. These include the virulence determinants ecotin, the omptin PgtE, and the SPI-2 regulator SsrB. The Tat-system and the PocR regulator that together promote anaerobic respiration of tetrathionate on 1,2-propanediol are also under direct CpxR control. Notably, 1,2-propanediol represses hilA expression. Thus, our work demonstrates for the first time the involvement of the Cpx system in a complex network mediating metabolism and virulence function. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/30716090/Contribution_of_the_Cpx_envelope_stress_system_to_metabolism_and_virulence_regulation_in_Salmonella_enterica_serovar_Typhimurium_ L2 - https://dx.plos.org/10.1371/journal.pone.0211584 DB - PRIME DP - Unbound Medicine ER -