Mark G Gorelik, Helen Yakhnin, Archana Pannuri, Alyssa C Walker, Christine Pourciau, Daniel Czyz, Tony Romeo, Paul Babitzke
{"title":"CsrA 对大肠杆菌极酸应激反应的多重调控。","authors":"Mark G Gorelik, Helen Yakhnin, Archana Pannuri, Alyssa C Walker, Christine Pourciau, Daniel Czyz, Tony Romeo, Paul Babitzke","doi":"10.1128/jb.00354-23","DOIUrl":null,"url":null,"abstract":"<p><p>CsrA is an RNA-binding protein that regulates processes critical for growth and survival, including central carbon metabolism, motility, biofilm formation, stress responses, and expression of virulence factors in pathogens. Transcriptomics studies in <i>Escherichia coli</i> suggested that CsrA repressed genes involved in surviving extremely acidic conditions. Here, we examine the effects of disrupting CsrA-dependent regulation on the expression of genes and circuitry for acid stress survival and demonstrate CsrA-mediated repression at multiple levels. We show that this repression is critical for managing the trade-off between growth and survival; overexpression of acid stress genes caused by <i>csrA</i> disruption enhances survival under extreme acidity but is detrimental for growth under mildly acidic conditions. <i>In vitro</i> studies confirmed that CsrA binds specifically to mRNAs of structural and regulatory genes for acid stress survival, causing translational repression. We also found that translation of the top-tier acid stress regulator, <i>evgA</i>, is coupled to that of a small leader peptide, <i>evgL</i>, which is repressed by CsrA. Unlike dedicated acid stress response genes, <i>csrA</i> and its sRNA antagonists, <i>csrB</i> and <i>csrC,</i> did not exhibit a substantial response to acid shock. Furthermore, disruption of CsrA regulation of acid stress genes impacted host-microbe interactions in <i>Caenorhabditis elegans</i>, alleviating GABA deficiencies. This study expands the known regulon of CsrA to genes of the extreme acid stress response of <i>E. coli</i> and highlights a new facet of the global role played by CsrA in balancing the opposing physiological demands of stress resistance with the capacity for growth and modulating host interactions.IMPORTANCETo colonize/infect the mammalian intestinal tract, bacteria must survive exposure to the extreme acidity of the stomach. <i>E. coli</i> does this by expressing proteins that neutralize cytoplasmic acidity and cope with molecular damage caused by low pH. Because of the metabolic cost of these processes, genes for surviving acid stress are tightly regulated. Here, we show that CsrA negatively regulates the cascade of expression responsible for the acid stress response. Increased expression of acid response genes due to <i>csrA</i> disruption improved survival at extremely low pH but inhibited growth under mildly acidic conditions. Our findings define a new layer of regulation in the acid stress response of <i>E. coli</i> and a novel physiological function for CsrA.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210196/pdf/","citationCount":"0","resultStr":"{\"title\":\"Multitier regulation of the <i>E. coli</i> extreme acid stress response by CsrA.\",\"authors\":\"Mark G Gorelik, Helen Yakhnin, Archana Pannuri, Alyssa C Walker, Christine Pourciau, Daniel Czyz, Tony Romeo, Paul Babitzke\",\"doi\":\"10.1128/jb.00354-23\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>CsrA is an RNA-binding protein that regulates processes critical for growth and survival, including central carbon metabolism, motility, biofilm formation, stress responses, and expression of virulence factors in pathogens. Transcriptomics studies in <i>Escherichia coli</i> suggested that CsrA repressed genes involved in surviving extremely acidic conditions. Here, we examine the effects of disrupting CsrA-dependent regulation on the expression of genes and circuitry for acid stress survival and demonstrate CsrA-mediated repression at multiple levels. We show that this repression is critical for managing the trade-off between growth and survival; overexpression of acid stress genes caused by <i>csrA</i> disruption enhances survival under extreme acidity but is detrimental for growth under mildly acidic conditions. <i>In vitro</i> studies confirmed that CsrA binds specifically to mRNAs of structural and regulatory genes for acid stress survival, causing translational repression. We also found that translation of the top-tier acid stress regulator, <i>evgA</i>, is coupled to that of a small leader peptide, <i>evgL</i>, which is repressed by CsrA. Unlike dedicated acid stress response genes, <i>csrA</i> and its sRNA antagonists, <i>csrB</i> and <i>csrC,</i> did not exhibit a substantial response to acid shock. Furthermore, disruption of CsrA regulation of acid stress genes impacted host-microbe interactions in <i>Caenorhabditis elegans</i>, alleviating GABA deficiencies. This study expands the known regulon of CsrA to genes of the extreme acid stress response of <i>E. coli</i> and highlights a new facet of the global role played by CsrA in balancing the opposing physiological demands of stress resistance with the capacity for growth and modulating host interactions.IMPORTANCETo colonize/infect the mammalian intestinal tract, bacteria must survive exposure to the extreme acidity of the stomach. <i>E. coli</i> does this by expressing proteins that neutralize cytoplasmic acidity and cope with molecular damage caused by low pH. Because of the metabolic cost of these processes, genes for surviving acid stress are tightly regulated. Here, we show that CsrA negatively regulates the cascade of expression responsible for the acid stress response. Increased expression of acid response genes due to <i>csrA</i> disruption improved survival at extremely low pH but inhibited growth under mildly acidic conditions. Our findings define a new layer of regulation in the acid stress response of <i>E. coli</i> and a novel physiological function for CsrA.</p>\",\"PeriodicalId\":15107,\"journal\":{\"name\":\"Journal of Bacteriology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-04-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210196/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Bacteriology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1128/jb.00354-23\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Bacteriology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/jb.00354-23","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/6 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Multitier regulation of the E. coli extreme acid stress response by CsrA.
CsrA is an RNA-binding protein that regulates processes critical for growth and survival, including central carbon metabolism, motility, biofilm formation, stress responses, and expression of virulence factors in pathogens. Transcriptomics studies in Escherichia coli suggested that CsrA repressed genes involved in surviving extremely acidic conditions. Here, we examine the effects of disrupting CsrA-dependent regulation on the expression of genes and circuitry for acid stress survival and demonstrate CsrA-mediated repression at multiple levels. We show that this repression is critical for managing the trade-off between growth and survival; overexpression of acid stress genes caused by csrA disruption enhances survival under extreme acidity but is detrimental for growth under mildly acidic conditions. In vitro studies confirmed that CsrA binds specifically to mRNAs of structural and regulatory genes for acid stress survival, causing translational repression. We also found that translation of the top-tier acid stress regulator, evgA, is coupled to that of a small leader peptide, evgL, which is repressed by CsrA. Unlike dedicated acid stress response genes, csrA and its sRNA antagonists, csrB and csrC, did not exhibit a substantial response to acid shock. Furthermore, disruption of CsrA regulation of acid stress genes impacted host-microbe interactions in Caenorhabditis elegans, alleviating GABA deficiencies. This study expands the known regulon of CsrA to genes of the extreme acid stress response of E. coli and highlights a new facet of the global role played by CsrA in balancing the opposing physiological demands of stress resistance with the capacity for growth and modulating host interactions.IMPORTANCETo colonize/infect the mammalian intestinal tract, bacteria must survive exposure to the extreme acidity of the stomach. E. coli does this by expressing proteins that neutralize cytoplasmic acidity and cope with molecular damage caused by low pH. Because of the metabolic cost of these processes, genes for surviving acid stress are tightly regulated. Here, we show that CsrA negatively regulates the cascade of expression responsible for the acid stress response. Increased expression of acid response genes due to csrA disruption improved survival at extremely low pH but inhibited growth under mildly acidic conditions. Our findings define a new layer of regulation in the acid stress response of E. coli and a novel physiological function for CsrA.
期刊介绍:
The Journal of Bacteriology (JB) publishes research articles that probe fundamental processes in bacteria, archaea and their viruses, and the molecular mechanisms by which they interact with each other and with their hosts and their environments.