Journal of Bacteriology最新文献

{"title":"Lighting the way: how the Vibrio fischeri model microbe reveals the complexity of Earth’s “simplest” life forms","authors":"Alecia N. Septer, Karen L. Visick","doi":"10.1128/jb.00035-24","DOIUrl":"https://doi.org/10.1128/jb.00035-24","url":null,"abstract":"Life is thought to have evolved in the ocean before expanding to terrestrial habitats.\u0000It is no wonder then that marine bacteria share genes, physiology, functional pathways,\u0000and regulatory mechanisms with their terrestrial cousins. These pathways and processes\u0000represent deeply rooted, conserved strategies that have evolved over billions of years\u0000and adapted to new habitats as the Earth and its increasingly diverse host species\u0000changed over time.","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted deletion of Pf prophages from diverse Pseudomonas aeruginosa isolates has differential impacts on quorum sensing and virulence traits","authors":"Amelia K. SchmidtCaleb M. SchwartzkopfJulie D. PourtoisElizabeth B. BurgenerDominick R. FaithAlex JoyceTyrza LammaGeetha KumarPaul L. BollykyPatrick R. Secor1Division of Biological Sciences, University of Montana, Missoula, Montana, USA2Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, USA3Division of Pediatric Pulmonology and Sleep Medicine, Children’s Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA4Center for Excellence in Pulmonary Biology, Department of Pediatrics, Stanford University, Stanford, California, USA5School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Kerala, India, Joseph Bondy-Denomy","doi":"10.1128/jb.00402-23","DOIUrl":"https://doi.org/10.1128/jb.00402-23","url":null,"abstract":"Journal of Bacteriology, Ahead of Print. <br/>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140827626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A flow equilibrium of zinc in cells of Cupriavidus metallidurans.","authors":"D. Nies, Grit Schleuder, Diana Galea, M. Herzberg","doi":"10.1128/jb.00080-24","DOIUrl":"https://doi.org/10.1128/jb.00080-24","url":null,"abstract":"The hypothesis was tested that a kinetical flow equilibrium of uptake and efflux reactions is responsible for balancing the cellular zinc content. The experiments were done with the metal-resistant bacterium Cupriavidus metallidurans. In pulse-chase experiments, the cells were loaded with radioactive 65Zn and chased with the 100-fold concentration of non-radioactive zinc chloride. In parallel, the cells were loaded with isotope-enriched stable 67Zn and chased with non-enriched zinc to differentiate between zinc pools in the cell. The experiments demonstrated the existence of a kinetical flow equilibrium, resulting in a constant turnover of cell-bound zinc ions. The absence of the metal-binding cytoplasmic components, polyphosphate and glutathione, metal uptake, and metal efflux systems influenced the flow equilibrium. The experiments also revealed that not all zinc uptake and efflux systems are known in C. metallidurans. Cultivation of the cells under zinc-replete, zinc-, and zinc-magnesium-starvation conditions influenced zinc import and export rates. Here, magnesium starvation had a stronger influence compared to zinc starvation. Other metal cations, especially cobalt, affected the cellular zinc pools and zinc export during the chase reaction. In summary, the experiments with 65Zn and 67Zn demonstrated a constant turnover of cell-bound zinc. This indicated that simultaneously occurring import and export reactions in combination with cytoplasmic metal-binding components resulted in a kinetical flow equilibrium that was responsible for the adjustment of the cellular zinc content.\u0000\u0000\u0000IMPORTANCE\u0000Understanding the biochemical action of a single enzyme or transport protein is the pre-requisite to obtain insight into its cellular function but this is only one half of the coin. The other side concerns the question of how central metabolic functions of a cell emerge from the interplay of different proteins and other macromolecules. This paper demonstrates that a flow equilibrium of zinc uptake and efflux reactions is at the core of cellular zinc homeostasis and identifies the most important contributors to this flow equilibrium: the uptake and efflux systems and metal-binding components of the cytoplasm.","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140657505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PmrAB, the two-component system of Acinetobacter baumannii, controls the phosphoethanolamine modification of lipooligosaccharide in response to metal ions.","authors":"Noriteru Yamada, Go Kamoshida, T. Shiraishi, Daiki Yamaguchi, Momoko Matsuoka, Reika Yamauchi, Nana Kanda, Roku Kamioka, Norihiko Takemoto, Yuji Morita, Masahiro Fujimuro, S. Yokota, Kinnosuke Yahiro","doi":"10.1128/jb.00435-23","DOIUrl":"https://doi.org/10.1128/jb.00435-23","url":null,"abstract":"Acinetobacter baumannii is highly resistant to antimicrobial agents, and XDR strains have become widespread. A. baumannii has developed resistance to colistin, which is considered the last resort against XDR Gram-negative bacteria, mainly caused by lipooligosaccharide (LOS) phosphoethanolamine (pEtN) and/or galactosamine (GalN) modifications induced by mutations that activate the two-component system (TCS) pmrAB. Although PmrAB of A. baumannii has been recognized as a drug resistance factor, its function as TCS, including its regulatory genes and response factors, has not been fully elucidated. In this study, to clarify the function of PmrAB as TCS, we elucidated the regulatory genes (regulon) of PmrAB via transcriptome analysis using pmrAB-activated mutant strains. We discovered that PmrAB responds to low pH, Fe2+, Zn2+, and Al3+. A. baumannii selectively recognizes Fe2+ rather than Fe3+, and a novel region ExxxE, in addition to the ExxE motif sequence, is involved in the environmental response. Furthermore, PmrAB participates in the phosphoethanolamine modification of LOS on the bacterial surface in response to metal ions such as Al3+, contributing to the attenuation of Al3+ toxicity and development of resistance to colistin and polymyxin B in A. baumannii. This study demonstrates that PmrAB in A. baumannii not only regulates genes that play an important role in drug resistance but is also involved in responses to environmental stimuli such as metal ions and pH, and this stimulation induces LOS modification. This study reveals the importance of PmrAB in the environmental adaptation and antibacterial resistance emergence mechanisms of A. baumannii.\u0000\u0000\u0000IMPORTANCE\u0000Antimicrobial resistance (AMR) is a pressing global issue in human health. Acinetobacter baumannii is notably high on the World Health Organization's list of bacteria for which new antimicrobial agents are urgently needed. Colistin is one of the last-resort drugs used against extensively drug-resistant (XDR) Gram-negative bacteria. However, A. baumannii has become increasingly resistant to colistin, primarily by modifying its lipooligosaccharide (LOS) via activating mutations in the two-component system (TCS) PmrAB. This study comprehensively elucidates the detailed mechanism of drug resistance of PmrAB in A. baumannii as well as its biological functions. Understanding the molecular biology of these molecules, which serve as drug resistance factors and are involved in environmental recognition mechanisms in bacteria, is crucial for developing fundamental solutions to the AMR problem.","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140658684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell envelope structural and functional contributions to antibiotic resistance in <i>Burkholderia cenocepacia</i>.","authors":"Andrew M Hogan, Anna Motnenko, A S M Zisanur Rahman, Silvia T Cardona","doi":"10.1128/jb.00441-23","DOIUrl":"10.1128/jb.00441-23","url":null,"abstract":"<p><p>Antibiotic activity is limited by the physical construction of the Gram-negative cell envelope. Species of the <i>Burkholderia cepacia</i> complex (Bcc) are known as intrinsically multidrug-resistant opportunistic pathogens with low permeability cell envelopes. Here, we re-examined a previously performed chemical-genetic screen of barcoded transposon mutants in <i>B. cenocepacia</i> K56-2, focusing on cell envelope structural and functional processes. We identified structures mechanistically important for resistance to singular and multiple antibiotic classes. For example, susceptibility to novobiocin, avibactam, and the LpxC inhibitor, PF-04753299, was linked to the BpeAB-OprB efflux pump, suggesting these drugs are substrates for this pump in <i>B. cenocepacia</i>. Defects in peptidoglycan precursor synthesis specifically increased susceptibility to cycloserine and revealed a new putative amino acid racemase, while defects in divisome accessory proteins increased susceptibility to multiple β-lactams. Additionally, disruption of the periplasmic disulfide bond formation system caused pleiotropic defects on outer membrane integrity and β-lactamase activity. Our findings highlight the layering of resistance mechanisms in the structure and function of the cell envelope. Consequently, we point out processes that can be targeted for developing antibiotic potentiators.IMPORTANCEThe Gram-negative cell envelope is a double-layered physical barrier that protects cells from extracellular stressors, such as antibiotics. The <i>Burkholderia</i> cell envelope is known to contain additional modifications that reduce permeability. We investigated <i>Burkholderia</i> cell envelope factors contributing to antibiotic resistance from a genome-wide view by re-examining data from a transposon mutant library exposed to an antibiotic panel. We identified susceptible phenotypes for defects in structures and functions in the outer membrane, periplasm, and cytoplasm. Overall, we show that resistance linked to the cell envelope is multifaceted and provides new targets for the development of antibiotic potentiators.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signaling through the <i>Salmonella</i> PbgA-LapB regulatory complex activates LpxC proteolysis and limits lipopolysaccharide biogenesis during stationary-phase growth.","authors":"Joshua A Mettlach, Melina B Cian, Medha Chakraborty, Zachary D Dalebroux","doi":"10.1128/jb.00308-23","DOIUrl":"10.1128/jb.00308-23","url":null,"abstract":"<p><p><i>Salmonella enterica</i> serovar Typhimurium (<i>S</i>. Typhimurium) controls lipopolysaccharide (LPS) biosynthesis by regulating proteolysis of LpxC, the rate-limiting enzyme and target of preclinical antibiotics. PbgA/YejM/LapC regulates LpxC levels and controls outer membrane (OM) LPS composition at the log-to-stationary phase transition. Suppressor substitutions in <u>L</u>PS <u>a</u>ssembly <u>p</u>rotein <u>B</u> (LapB/YciM) rescue the LPS and OM integrity defects of <i>pbgA</i>-mutant <i>S</i>. Typhimurium. We hypothesized that PbgA regulates LpxC proteolysis by controlling LapB's ability to bind LpxC as a function of the growth phase. According to existing models, when nutrients are abundant, PbgA binds and restricts LapB from interacting with LpxC and FtsH, which limits LpxC proteolysis. However, when nutrients are limited, there is debate whether LapB dissociates from PbgA to bind LpxC and FtsH to enhance degradation. We sought to examine these models and investigate how the structure of LapB enables salmonellae to control LpxC proteolysis and LPS biosynthesis. Salmonellae increase LapB levels during the stationary phase to promote LpxC degradation, which limits lipid A-core production and increases their survival. The deletion of <i>lapB</i>, resulting in unregulated lipid A-core production and LpxC overabundance, leads to bacterial growth retardation. Tetratricopeptide repeats near the cytosol-inner membrane interface are sufficient for LapB to bind LpxC, and remarkably, LapB and PbgA interact in both growth phases, yet LpxC only associates with LapB in the stationary phase. Our findings support that PbgA-LapB exists as a constitutive complex in <i>S</i>. Typhimurium, which differentially binds LpxC to control LpxC proteolysis and limit lipid A-core biosynthesis in response to changes in the environment.IMPORTANCEAntimicrobial resistance has been a costly setback for human health and agriculture. Continued pursuit of new antibiotics and targets is imperative, and an improved understanding of existing ones is necessary. LpxC is an essential target of preclinical trial antibiotics that can eliminate multidrug-resistant Gram-negative bacterial infections. LapB is a natural LpxC inhibitor that targets LpxC for degradation and limits lipopolysaccharide production in Enterobacteriaceae. Contrary to some studies, findings herein support that LapB remains in complex instead of dissociating from its presumed negative regulator, PbgA/YejM/LapC, under conditions where LpxC proteolysis is enhanced. Advanced comprehension of this critical protein-lipid signaling network will lead to future development and refinement of small molecules that can specifically interfere.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"We have a community problem.","authors":"George A O'Toole","doi":"10.1128/jb.00073-24","DOIUrl":"10.1128/jb.00073-24","url":null,"abstract":"","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Proteus mirabilis</i> UreR coordinates cellular functions required for urease activity.","authors":"Madison J Fitzgerald, Melanie M Pearson, Harry L T Mobley","doi":"10.1128/jb.00031-24","DOIUrl":"10.1128/jb.00031-24","url":null,"abstract":"<p><p>A hallmark of <i>Proteus mirabilis</i> infection of the urinary tract is the formation of stones. The ability to induce urinary stone formation requires urease, a nickel metalloenzyme that hydrolyzes urea. This reaction produces ammonia as a byproduct, which can serve as a nitrogen source and weak base that raises the local pH. The resulting alkalinity induces the precipitation of ions to form stones. Transcriptional regulator UreR activates expression of urease genes in a urea-dependent manner. Thus, urease genes are highly expressed in the urinary tract where urea is abundant. Production of mature urease also requires the import of nickel into the cytoplasm and its incorporation into the urease apoenzyme. Urease accessory proteins primarily acquire nickel from one of two nickel transporters and facilitate incorporation of nickel to form mature urease. In this study, we performed a comprehensive RNA-seq to define the <i>P. mirabilis</i> urea-induced transcriptome as well as the UreR regulon. We identified UreR as the first defined regulator of nickel transport in <i>P. mirabilis</i>. We also offer evidence for the direct regulation of the Ynt nickel transporter by UreR. Using bioinformatics, we identified UreR-regulated urease loci in 15 <i>Morganellaceae</i> family species across three genera. Additionally, we located two mobilized UreR-regulated urease loci that also encode the <i>ynt</i> transporter, implying that UreR regulation of nickel transport is a conserved regulatory relationship. Our study demonstrates that UreR specifically regulates genes required to produce mature urease, an essential virulence factor for <i>P. mirabilis</i> uropathogenesis.</p><p><strong>Importance: </strong>Catheter-associated urinary tract infections (CAUTIs) account for over 40% of acute nosocomial infections in the USA and generate $340 million in healthcare costs annually. A major causative agent of CAUTIs is <i>Proteus mirabilis</i>, an understudied Gram-negative pathogen noted for its ability to form urinary stones via the activity of urease. Urease mutants cannot induce stones and are attenuated in a murine UTI model, indicating this enzyme is essential to <i>P. mirabilis</i> pathogenesis. Transcriptional regulation of urease genes by UreR is well established; here, we expand the UreR regulon to include regulation of nickel import, a function required to produce mature urease. Furthermore, we reflect on the role of urea catalysis in <i>P. mirabilis</i> metabolism and provide evidence for its importance.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gliding motility proteins GldJ and SprB contribute to <i>Flavobacterium columnare</i> virulence.","authors":"Nicole C Thunes, Jason P Evenhuis, Ryan S Lipscomb, David Pérez-Pascual, Rebecca J Stevick, Clayton Birkett, Jean-Marc Ghigo, Mark J McBride","doi":"10.1128/jb.00068-24","DOIUrl":"10.1128/jb.00068-24","url":null,"abstract":"<p><p><i>Flavobacterium columnare</i> causes columnaris disease in fish. Columnaris disease is incompletely understood, and adequate control measures are lacking. The type IX secretion system (T9SS) is required for <i>F. columnare</i> gliding motility and virulence. The T9SS and gliding motility machineries share some, but not all, components. GldN (required for gliding and for secretion) and PorV (involved in secretion but not required for gliding) are both needed for virulence, implicating T9SS-mediated secretion in virulence. The role of motility in virulence is uncertain. We constructed and analyzed <i>sprB</i>, <i>sprF</i>, and <i>gldJ</i> mutants that were defective for motility but that maintained T9SS function to understand the role of motility in virulence. Wild-type cells moved rapidly and formed spreading colonies. In contrast, <i>sprB</i> and <i>sprF</i> deletion mutants were partially defective in gliding and formed nonspreading colonies. Both mutants exhibited reduced virulence in rainbow trout fry. A <i>gldJ</i> deletion mutant was nonmotile, secretion deficient, and avirulent in rainbow trout fry. To separate the roles of GldJ in secretion and in motility, we generated <i>gldJ</i> truncation mutants that produce nearly full-length GldJ. Mutant <i>gldJ</i>₅₆₃, which produces GldJ truncated at amino acid 563, was defective for gliding but was competent for secretion as measured by extracellular proteolytic activity. This mutant displayed reduced virulence in rainbow trout fry, suggesting that motility contributes to virulence. Fish that survived exposure to the <i>sprB</i> deletion mutant or the <i>gldJ</i>₅₆₃ mutant exhibited partial resistance to later challenge with wild-type cells. The results aid our understanding of columnaris disease and may suggest control strategies.IMPORTANCE<i>Flavobacterium columnare</i> causes columnaris disease in many species of freshwater fish in the wild and in aquaculture systems. Fish mortalities resulting from columnaris disease are a major problem for aquaculture. <i>F. columnare</i> virulence is incompletely understood, and control measures are inadequate. Gliding motility and protein secretion have been suggested to contribute to columnaris disease, but evidence directly linking motility to disease was lacking. We isolated and analyzed mutants that were competent for secretion but defective for motility. Some of these mutants exhibited decreased virulence. Fish that had been exposed to these mutants were partially protected from later exposure to the wild type. The results contribute to our understanding of columnaris disease and may aid development of control strategies.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"10.1128/jb.00354-23","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":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}