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CpxR/CpxA Controls scsABCD Transcription To Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium.
J Bacteriol. 2018 08 15; 200(16)JB

Abstract

Periplasmic thiol/disulfide oxidoreductases participate in the formation and isomerization of disulfide bonds and contribute to the virulence of pathogenic microorganisms. Among the systems encoded in the Salmonella genome, the system encoded by the scsABCD locus was shown to be required to cope with Cu and H2O2 stress. Here we report that this locus forms an operon whose transcription is driven by a promoter upstream of scsA and depends on CpxR/CpxA and on Cu. Furthermore, genes homologous to scsB, scsC, and scsD are always detected immediately downstream of scsA and in the same genetic arrangement in all scsA-harboring enterobacterial species. Also, a CpxR-binding site is detected upstream of scsA in most of those species, providing evidence of evolutionarily conserved function and regulation. Each individual scs gene shows a different role in copper and/or H2O2 resistance, indicating hierarchical contributions of these factors in the defense against these intoxicants. A protective effect of Cu preincubation against H2O2 toxicity and the increased Cu-mediated activation of cpxP in the ΔscsABCD mutant suggest that the CpxR/CpxA-controlled transcription of the ScsABCD system contributes to prevent Cu toxicity and to restore the redox balance at the Salmonella envelope.IMPORTANCE Copper intoxication triggers both specific and nonspecific responses in Salmonella The scs locus, which codes for periplasmic thiol/disulfide-oxidoreductase/isomerase-like proteins, has been the focus of attention because it is necessary for copper resistance, oxidative stress responses, and virulence and because it is not present in nonpathogenic Escherichia coli Still, the conditions under which the scs locus is expressed and the roles of its individual components remain unknown. In this report, we examine the contribution of each Scs factor to survival under H2O2 and copper stress. We establish that the scs genes form a copper-activated operon controlled by the CpxR/CpxA signal transduction system, and we provide evidence of its conserved gene arrangement and regulation in other bacterial pathogens.

Authors+Show Affiliations

Instituto de Biología Molecular y Celular de Rosario, Universidad Nacional de Rosario-CONICET, Rosario, Argentina. Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.Instituto de Biología Molecular y Celular de Rosario, Universidad Nacional de Rosario-CONICET, Rosario, Argentina. Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.Instituto de Biología Molecular y Celular de Rosario, Universidad Nacional de Rosario-CONICET, Rosario, Argentina soncini@ibr-conicet.gov.ar. Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.

Pub Type(s)

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

Language

eng

PubMed ID

29866803

Citation

López, Carolina, et al. "CpxR/CpxA Controls scsABCD Transcription to Counteract Copper and Oxidative Stress in Salmonella Enterica Serovar Typhimurium." Journal of Bacteriology, vol. 200, no. 16, 2018.
López C, Checa SK, Soncini FC. CpxR/CpxA Controls scsABCD Transcription To Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium. J Bacteriol. 2018;200(16).
López, C., Checa, S. K., & Soncini, F. C. (2018). CpxR/CpxA Controls scsABCD Transcription To Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium. Journal of Bacteriology, 200(16). https://doi.org/10.1128/JB.00126-18
López C, Checa SK, Soncini FC. CpxR/CpxA Controls scsABCD Transcription to Counteract Copper and Oxidative Stress in Salmonella Enterica Serovar Typhimurium. J Bacteriol. 2018 08 15;200(16) PubMed PMID: 29866803.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CpxR/CpxA Controls scsABCD Transcription To Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium. AU - López,Carolina, AU - Checa,Susana K, AU - Soncini,Fernando C, Y1 - 2018/07/25/ PY - 2018/03/02/received PY - 2018/05/25/accepted PY - 2018/6/6/pubmed PY - 2019/9/17/medline PY - 2018/6/6/entrez KW - CpxRA KW - ScsABCD KW - copper resistance KW - envelope homeostasis KW - oxidative stress KW - thioredoxin-like proteins JF - Journal of bacteriology JO - J Bacteriol VL - 200 IS - 16 N2 - Periplasmic thiol/disulfide oxidoreductases participate in the formation and isomerization of disulfide bonds and contribute to the virulence of pathogenic microorganisms. Among the systems encoded in the Salmonella genome, the system encoded by the scsABCD locus was shown to be required to cope with Cu and H2O2 stress. Here we report that this locus forms an operon whose transcription is driven by a promoter upstream of scsA and depends on CpxR/CpxA and on Cu. Furthermore, genes homologous to scsB, scsC, and scsD are always detected immediately downstream of scsA and in the same genetic arrangement in all scsA-harboring enterobacterial species. Also, a CpxR-binding site is detected upstream of scsA in most of those species, providing evidence of evolutionarily conserved function and regulation. Each individual scs gene shows a different role in copper and/or H2O2 resistance, indicating hierarchical contributions of these factors in the defense against these intoxicants. A protective effect of Cu preincubation against H2O2 toxicity and the increased Cu-mediated activation of cpxP in the ΔscsABCD mutant suggest that the CpxR/CpxA-controlled transcription of the ScsABCD system contributes to prevent Cu toxicity and to restore the redox balance at the Salmonella envelope.IMPORTANCE Copper intoxication triggers both specific and nonspecific responses in Salmonella The scs locus, which codes for periplasmic thiol/disulfide-oxidoreductase/isomerase-like proteins, has been the focus of attention because it is necessary for copper resistance, oxidative stress responses, and virulence and because it is not present in nonpathogenic Escherichia coli Still, the conditions under which the scs locus is expressed and the roles of its individual components remain unknown. In this report, we examine the contribution of each Scs factor to survival under H2O2 and copper stress. We establish that the scs genes form a copper-activated operon controlled by the CpxR/CpxA signal transduction system, and we provide evidence of its conserved gene arrangement and regulation in other bacterial pathogens. SN - 1098-5530 UR - https://www.unboundmedicine.com/medline/citation/29866803/CpxR/CpxA_Controls_scsABCD_Transcription_To_Counteract_Copper_and_Oxidative_Stress_in_Salmonella_enterica_Serovar_Typhimurium_ L2 - http://jb.asm.org/cgi/pmidlookup?view=long&pmid=29866803 DB - PRIME DP - Unbound Medicine ER -