CpxR/CpxA Controls scsABCD Transcription To Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium
CpxR/CpxA Controls scsABCD Transcription To Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium
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DOI：
10.1128/jb.00126-18
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发表时间：
2018-08-01
影响因子：
3.2
通讯作者：
Soncini, Fernando C.
中科院分区：
文献类型：
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作者：
Lopez, Carolina;Checa, Susana K.;Soncini, Fernando C.
周质硫醇/二硫键氧化还原酶参与二硫键的形成和异构化，有助于病原微生物的毒力。在沙门氏菌基因组编码的系统中，由scsABCD基因编码的系统被证明是应对铜和H_2O_2胁迫所必需的。在这里，我们报告该基因座形成一个操纵子，其转录由SCSA上游的启动子驱动，并依赖于CpxR/CpxA和铜。此外，与SCSB、SCSC和SCSD同源的基因总是在SCSA的下游被检测到，并且在所有含有SCSA的肠道细菌物种中以相同的遗传排列被检测到。此外，在大多数物种的SCSA上游检测到CpxR结合位点，这为进化上保守的功能和调控提供了证据。每个单独的SCS基因在铜和/或H_2O_2抗性中显示出不同的作用，表明这些因子在防御这些毒物中起着不同的作用。铜预先孵育对H_2O_2毒性的保护作用和在Delta scsABCD突变体中铜介导的cpxP活性的增加表明，CpxR/CpxA控制的ScsABCD系统转录有助于防止铜毒性并恢复沙门氏菌包膜的氧化还原平衡。编码周质硫醇/二硫代氧化还原酶/异构酶样蛋白的SCS基因座一直是人们关注的焦点，因为它是铜抗性、氧化应激反应和毒力所必需的，而且在非致病性大肠杆菌中不存在。尽管如此，SCS基因表达的条件及其各个组成部分的作用仍是未知的。在这份报告中，我们研究了在过氧化氢和铜胁迫下每个SCS因子对生存的贡献。我们证实SCS基因形成一个受CpxR/CpxA信号转导系统控制的铜激活操纵子，并为其在其他细菌病原体中的保守基因排列和调控提供了证据。
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 Delta scsABCD 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.