Molecular Microbiology最新文献_第10页

Cyclic Di-AMP Affects Cell Membrane Integrity of Streptococcus pneumoniae. 环二磷酸腺苷对肺炎链球菌细胞膜完整性的影响

IF 2.6 2区生物学

Molecular Microbiology Pub Date : 2025-09-01 Epub Date: 2025-06-27 DOI: 10.1111/mmi.70003

Tiffany M Zarrella, Jianle Gao, Nathan Forrest, Elijah Crosbourne, Kaibo Cui, Guangchun Bai

{"title":"Cyclic Di-AMP Affects Cell Membrane Integrity of Streptococcus pneumoniae.","authors":"Tiffany M Zarrella, Jianle Gao, Nathan Forrest, Elijah Crosbourne, Kaibo Cui, Guangchun Bai","doi":"10.1111/mmi.70003","DOIUrl":"10.1111/mmi.70003","url":null,"abstract":"Competence is an important bioprocess for Streptococcus pneumoniae. Previously, we demonstrated that the bacterial second messenger cyclic di-adenosine monophosphate (c-di-AMP) modulates pneumococcal competence. Surprisingly, cdaA*, a strain producing less c-di-AMP due to a point mutation in the diadenylate cyclase CdaA, is susceptible to competence-stimulating peptide (CSP). In this study, we screened cdaA* suppressor mutants resistant to CSP to explore the underlying mechanism. Of 14 clones sequenced, nine clones possessed mutations in the c-di-AMP phosphodiesterase Pde1, indicating that the susceptibility to CSP of the cdaA* strain is correlated to c-di-AMP levels. Another two clones exhibited a mutation in FabT, a transcription factor controlling cell membrane fatty acid biosynthesis. We further showed that deletion of fabT, disruption of the FabT-binding site within the PfabK promoter, deletion of a fabT activator BriC, or disruption of K+ uptake in the cdaA* mutant all rescued the growth defect of the cdaA* strain in media supplemented with CSP. Finally, we found that a c-di-AMP phosphodiesterase-null mutant with high levels of c-di-AMP is highly sensitive to treatment with either ethanol or Triton X-100, which could be corrected by reducing c-di-AMP levels through introducing point mutations in CdaA. Together, these findings indicate that c-di-AMP affects cell membrane integrity.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"230-244"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An HWE-Family Histidine Kinase Modulates Brucella Cell Envelope Properties and Host Innate Immune Response. hwe家族组氨酸激酶调节布鲁氏菌细胞包膜特性和宿主先天免疫反应。

IF 2.6 2区生物学

Molecular Microbiology Pub Date : 2025-09-01 Epub Date: 2025-06-26 DOI: 10.1111/mmi.70006

Xingru Chen, Emily Perez, Eleanor C Scheeres, Rosemary Northcote, Aretha Fiebig, Andrew J Olive, Sean Crosson

{"title":"An HWE-Family Histidine Kinase Modulates Brucella Cell Envelope Properties and Host Innate Immune Response.","authors":"Xingru Chen, Emily Perez, Eleanor C Scheeres, Rosemary Northcote, Aretha Fiebig, Andrew J Olive, Sean Crosson","doi":"10.1111/mmi.70006","DOIUrl":"10.1111/mmi.70006","url":null,"abstract":"The bacterial cell envelope is essential for viability and host interaction. In the intracellular pathogen Brucella ovis, the orphan HWE-family histidine kinase PhyK has been implicated in processes that influence cell envelope homeostasis, yet its function remains largely uncharacterized. We show that deletion of phyK (∆phyK) disrupts cell size control, increases resistance to anionic detergents, enhances sensitivity to cationic envelope disruptors, and triggers broad transcriptional changes, including reduced expression of aerobic respiration genes and increased expression of genes involved in transport and lipid metabolism. This transcriptional profile mirrors that of wild-type B. ovis exposed to an anionic detergent, indicating that loss of PhyK function primes cells to resist this stress. Despite its altered cell envelope properties, the ∆phyK mutant exhibits no fitness defect in ex vivo macrophage infection models. However, it elicits a significantly reduced pro-inflammatory cytokine response in activated murine macrophages compared to the wild-type strain. We further show that purified PhyK can form multiple stable oligomeric species in solution, reflecting the structural plasticity observed in other HWE-family kinases and likely contributing to its signaling function in vivo. Our results establish PhyK as a key regulator of B. ovis cell envelope properties that can modulate host immune interactions.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"245-258"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defining the Enterococcus faecalis Fatty Acid Kinase System of Exogeneous Fatty Acid Utilization 确定粪肠球菌脂肪酸激酶系统的外源性脂肪酸利用

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2025-08-02 DOI: 10.1111/mmi.70017

Huijuan Dong, Qi Zou, John E. Cronan

{"title":"Defining the Enterococcus faecalis Fatty Acid Kinase System of Exogeneous Fatty Acid Utilization","authors":"Huijuan Dong, Qi Zou, John E. Cronan","doi":"10.1111/mmi.70017","DOIUrl":"https://doi.org/10.1111/mmi.70017","url":null,"abstract":"Phospholipid synthesis in Firmicute bacteria differs markedly from that of the paradigm Escherichia coli pathway in that acyl phosphates are a key intermediate. Acyl phosphates are required for the first acylation step of the phospholipid synthesis pathway catalyzed by the PlsY acyltransferase and are synthesized by two different pathways. In the absence of exogenous fatty acids, de novo synthesized acyl‐acyl carrier protein (ACP) species are converted to acyl phosphates by the PlsX acyl‐ACP: phosphate acyltransferase, which transfers the acyl chain from ACP to inorganic phosphate. When exogenous fatty acids are present, these acids are converted to acyl phosphates by the FakAB fatty acid kinase and can be converted to acyl‐ACPs via PlsX. The active kinase is composed of the ATP‐requiring FakA subunit and a FakB fatty acid binding protein, which acts to present the fatty acid carboxyl group to the FakA kinase active site. In all Firmicutes examined to date, multiple FakB species are present. Staphylococcus aureus has two, whereas Streptococcus pneumoniae has three, whereas Enterococcus faecalis encodes four FakB proteins. We report the fatty acid preferences of these proteins obtained by use of mutant strains lacking each FakB or all possible combinations of three FakB deletions, plus a strain lacking all four FakB proteins. We also report the phenotype of a ∆fakA strain and of a ∆fakA bypass suppressor mutant, plus the first indication of a role of the FakAB pathway in recycling of acyl chains.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"13 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Flagellin-Specific Chaperone FliS of Borrelia burgdorferi Controls the Cytoplasmic Pool of Flagellins at the Level of Translation Initiation, Secretion, and Proteolysis. 伯氏疏螺旋体鞭毛蛋白特异性伴侣FliS在翻译起始、分泌和蛋白水解水平上控制鞭毛蛋白的细胞质池。

IF 3.1 2区生物学

Molecular Microbiology Pub Date : 2025-08-01 Epub Date: 2025-06-09 DOI: 10.1111/mmi.15380

Ching Wooen Sze, Kai Zhang, Michael J Lynch, Wangbiao Guo, Jun Liu, Brian R Crane, Chunhao Li

{"title":"The Flagellin-Specific Chaperone FliS of Borrelia burgdorferi Controls the Cytoplasmic Pool of Flagellins at the Level of Translation Initiation, Secretion, and Proteolysis.","authors":"Ching Wooen Sze, Kai Zhang, Michael J Lynch, Wangbiao Guo, Jun Liu, Brian R Crane, Chunhao Li","doi":"10.1111/mmi.15380","DOIUrl":"10.1111/mmi.15380","url":null,"abstract":"The flagellin-specific chaperone FliS has been studied in externally flagellated bacteria; however, its role in spirochetes, a group of bacteria that possess unique internalized flagella (termed endo- or periplasmic flagella), remains unexplored. Here, we investigate the function of FliS in the Lyme disease spirochete Borrelia burgdorferi . Using loss-of-function studies, combined with biochemical assays and cryo-electron tomography, we demonstrate that FliS deletion selectively reduces FlaB expression, the major flagellin protein, resulting in non-motile mutants with defective flagellar filaments. Mechanistically, we show that FlaB interacts with both FliS and FliW, the latter being an allosteric repressor of the RNA-binding protein CsrA, which inhibits FlaB translation. These four components form a regulatory circuit that fine-tunes FlaB levels and flagellar assembly via a partner-switching mechanism. Deletion of fliS disrupts FlaB secretion, leading to its cytoplasmic accumulation, sequestration of FliW, and subsequent release of CsrA to suppress FlaB synthesis. Accumulation of cytoplasmic FlaB also triggers its degradation to prevent toxicity. Our findings reveal a post-transcriptional regulatory mechanism governing flagellar assembly in B. burgdorferi , an evolutionary outlier that lacks the canonical transcriptional cascade controlling flagellar biosynthesis in most bacteria.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"173-187"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12327847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homeostatic Influence of Fig4 Outside of the Fab1‐Vac14‐Fig4 Complex in Saccharomyces cerevisiae Fab1‐Vac14‐Fig4复合物外部对酿酒酵母体内稳态的影响

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2025-07-31 DOI: 10.1111/mmi.70018

Hannah E. Reeves, Anna King, Imran Khan, Asha Thomas, Corey Chung, Anirudan Sivaprakash, Harrison A. Hall, Cole McGuire, Victoria Cruz, Alim Habib, Lauren Dotson, Sophia R. Lee, Caroline L. Darbro, Bethany S. Strunk

{"title":"Homeostatic Influence of Fig4 Outside of the Fab1‐Vac14‐Fig4 Complex in Saccharomyces cerevisiae","authors":"Hannah E. Reeves, Anna King, Imran Khan, Asha Thomas, Corey Chung, Anirudan Sivaprakash, Harrison A. Hall, Cole McGuire, Victoria Cruz, Alim Habib, Lauren Dotson, Sophia R. Lee, Caroline L. Darbro, Bethany S. Strunk","doi":"10.1111/mmi.70018","DOIUrl":"https://doi.org/10.1111/mmi.70018","url":null,"abstract":"The lipid phosphatase Fig4 is conserved in all eukaryotes and is associated with human neurological diseases for which there are currently no specific therapies. Fig4 functions in both the production and turnover of its lipid substrate, PI3,5P2, through participation in the Fab1‐Vac14‐Fig4 complex with its opposing kinase Fab1. The molecular mechanisms through which Fig4 influences PI3,5P2 production are not fully understood but are believed to require Fig4 binding to the scaffold protein Vac14. We unexpectedly found that multiple Fig4 disease‐related mutants that are impaired in binding to the Fab1‐Vac14‐Fig4 complex dominantly confer tolerance to rapamycin, an inhibitor of the Target of Rapamycin Complex 1 (TORC1), when expressed in Saccharomyces cerevisiae. Fig4‐dependent rapamycin tolerance is conferred under moderate heat stress, independent of Vac14 and Fig4 catalytic activity. Conversely, expression of catalytically dead Fig4 that binds stably to the Fab1‐Vac14‐Fig4 complex enhances rapamycin sensitivity. We propose that Fig4 disease‐related mutants alter TORC1 signaling through gain of function under these conditions through an abnormal or sustained interaction with an unknown factor, perhaps by altering PI3,5P2 production. Investigation of the mechanisms whereby Fig4 mutants alter rapamycin tolerance may provide new insights into Fig4 molecular functions with potential relevance for Fig4‐related diseases.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"717 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Monofunctional FMN Riboswitch-Binding Regulator RibR From Bacillus amyloliquefaciens Promotes Riboflavin Biosynthesis. 来自解淀粉芽孢杆菌的单功能FMN核糖开关结合调节剂RibR促进核黄素的生物合成。

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2025-07-23 DOI: 10.1111/mmi.70015

Anna Hübenthal,Matthias Mack

{"title":"The Monofunctional FMN Riboswitch-Binding Regulator RibR From Bacillus amyloliquefaciens Promotes Riboflavin Biosynthesis.","authors":"Anna Hübenthal,Matthias Mack","doi":"10.1111/mmi.70015","DOIUrl":"https://doi.org/10.1111/mmi.70015","url":null,"abstract":"Flavin mononucleotide (FMN) riboswitches are RNA-based regulatory elements found in many bacteria. FMN riboswitches control genes responsible for the biosynthesis and transport of riboflavin (rib genes). Riboflavin (vitamin B2) is the precursor of the flavoenzyme cofactors FMN and flavin adenine dinucleotide (FAD), and it is FMN (not riboflavin or FAD) that is perceived by FMN riboswitches as a signal with regard to flavin homeostasis. When FMN levels are adequate, expression of rib genes is shut down by FMN riboswitches. The bifunctional protein RibR from the Gram-positive bacterium Bacillus subtilis contains an enzymatic and a regulatory part and is induced when cells encounter specific sulfur sources. Under these conditions, B. subtilis RibR binds to FMN riboswitches, overrides their genetic decisions, and stimulates rib gene expression. In B. subtilis, the objective of this RibR-mediated superordinate control is to link sulfur metabolism to riboflavin metabolism. B. subtilis RibR was previously the only known riboswitch-modulating protein. We now report on a similar but monofunctional protein from Bacillus amyloliquefaciens. RibR from B. amyloliquefaciens contains a regulatory/RNA-binding part only, and ribR expression is not stimulated by sulfur sources but by the disulfide-generating and oxidative stress-inducing compound diamide. RibR-like regulator proteins may be more widespread than anticipated and apparently have evolved to connect riboswitch-controlled pathways to other pathways.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"19 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autophagy and the Mitochondrial Lon1 Protease Are Necessary for Botrytis cinerea Heat Adaptation. 灰葡萄孢热适应需要自噬和线粒体Lon1蛋白酶。

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2025-07-18 DOI: 10.1111/mmi.70014

Mingzhe Zhang,Liang Ma,Zhiqun Lyu,Naomi Kagan Trushina,Amir Sharon

引用次数: 0

Filamentation Profiling Reveals Multiple Transcription Regulators Contributing to the Differences Between Candida albicans and Candida dubliniensis. 白色念珠菌和都柏林念珠菌之间的差异是由多种转录调控因子引起的。

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2025-07-17 DOI: 10.1111/mmi.70012

Teresa Meza-Davalos,Luis F García-Ortega,Eugenio Mancera

{"title":"Filamentation Profiling Reveals Multiple Transcription Regulators Contributing to the Differences Between Candida albicans and Candida dubliniensis.","authors":"Teresa Meza-Davalos,Luis F García-Ortega,Eugenio Mancera","doi":"10.1111/mmi.70012","DOIUrl":"https://doi.org/10.1111/mmi.70012","url":null,"abstract":"Candida dubliniensis is the most closely related species to C. albicans, one of the leading causes of fungal infections in humans. However, despite sharing many characteristics, C. dubliniensis is significantly less pathogenic. To better understand the molecular underpinnings of these dissimilarities, we focused on the regulation of filamentation, a developmental trait fundamental for host colonization. We generated a collection of 44 C. dubliniensis null mutants of transcription regulators whose orthologs in C. albicans had been previously implicated in filamentous growth. These regulators are very similar at the sequence level, but phenotypic screening identified several mutants with contrasting interspecific filamentation phenotypes beyond previously known differences. Bcr1, a well-known regulator of biofilm formation, stands out as its mutant mainly showed a filamentation defect in C. dubliniensis. Phenotypic and transcriptional characterization showed that the bcr1 defect is condition dependent and that this regulator plays a central role in the filamentation of C. dubliniensis, possibly by regulating the hyphal activator Ume6. Overall, our results suggest that several regulatory pathways are involved in the filamentation differences between C. albicans and C. dubliniensis and show that the C. dubliniensis mutant collection is a valuable resource to compare, at a molecular level, these species of medical relevance.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"7 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enzymatic and Structural Roles of Candida albicans Rev1 in DNA Damage Response and Disseminated Candidiasis. 白色念珠菌Rev1在DNA损伤反应和播散性念珠菌病中的酶和结构作用。

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2025-07-17 DOI: 10.1111/mmi.70013

Satya Ranjan Sahu,Sushree Subhashree Parida,Bhabasha Gyanadeep Utkalaja,Shreenath Nayak,Amrita Dalei,Narottam Acharya

{"title":"Enzymatic and Structural Roles of Candida albicans Rev1 in DNA Damage Response and Disseminated Candidiasis.","authors":"Satya Ranjan Sahu,Sushree Subhashree Parida,Bhabasha Gyanadeep Utkalaja,Shreenath Nayak,Amrita Dalei,Narottam Acharya","doi":"10.1111/mmi.70013","DOIUrl":"https://doi.org/10.1111/mmi.70013","url":null,"abstract":"Translesion DNA synthesis (TLS) is a fundamental biological process that enables DNA replication through various lesions to ensure genome stability and to prevent cell death due to replication fork collapse. Rev1, a member of Y-family DNA polymerase (Pol), functions in concert with a B-family enzyme Polζ in promoting TLS through various lesions. Interestingly, for such a function, the catalytic activity of Rev1 seems to be dispensable in Saccharomyces cerevisiae. Unlike Polζ, which possesses robust DNA polymerase activity, biochemical assays suggest that Rev1 predominantly incorporates a \"C\" opposite any templating residues, but the biological relevance of this activity of Rev1 remains elusive. Here we characterized Rev1 from Candida albicans, an opportunistic fungal pathogen responsible for maximum casualties due to systemic candidiasis in immunosuppressed individuals. Concerted genetic analyses of several Rev1 mutants in various DNA-damaging conditions suggested that in most lesion bypasses except 4-NQO-induced DNA lesions, the catalytic role of Rev1 is not important. However, simultaneous interactions of BRCT and the C-terminal domain of Rev1 with PCNA and Polζ, respectively, enable Rev1 to be essential during TLS. DNA damage recovery and mutagenesis assays further confirmed the lesion-specific roles of various domains of Rev1. Contrary to ex vivo data, animal studies suggested that CaRev1 is dispensable for systemic candidiasis development. We discuss the possible involvement of other TLS DNA polymerases in DNA damage response while C. albicans replicates and establishes itself in the host.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"13 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of a Novel RNA Polymerase Mutant of Escherichia coli That Confers Thermotolerance and Chaperone Independence 一种具有耐热性和伴侣独立性的新型大肠杆菌RNA聚合酶突变体的鉴定

IF 3.6 2区生物学

Molecular Microbiology Pub Date : 2025-07-10 DOI: 10.1111/mmi.70011

Melody Yeh, Keilen Kelly, Rajeev Misra

{"title":"Characterization of a Novel RNA Polymerase Mutant of Escherichia coli That Confers Thermotolerance and Chaperone Independence","authors":"Melody Yeh, Keilen Kelly, Rajeev Misra","doi":"10.1111/mmi.70011","DOIUrl":"https://doi.org/10.1111/mmi.70011","url":null,"abstract":"Bacterial cells activate stress‐sensing and stress‐mitigating pathways by employing a number of transcription regulators, some of which can bind directly to RNA polymerase to activate stress‐specific response pathways. However, mutations in the RNA polymerase genes can accumulate under certain selection conditions and activate stress‐mitigating pathways in a manner that is partly independent of pathway‐specific regulators. In this study, we characterized a novel mutation in the rpoB gene that transforms RNA polymerase into a “stringent” polymerase in the absence of one of the key stringent response (SR) activating factors (p)ppGpp, produced by the relA gene product. The mutant RNA polymerase allele, rpoB58, elevated thermotolerance and permitted growth without the key molecular chaperones (DnaKJ) and proteases (Lon, ClpP) at temperatures nonpermissive to cells expressing the wild type RNA polymerase genes. Remarkably, rpoB58 also reversed the cell division defect of ΔdnaJ at a nonpermissive temperature but could not overcome its lambda phage‐resistant phenotype. The rpoB58‐mediated rescue of the ΔdnaKJ growth defect was partly reversed in the absence of DksA, a protein that acts synergistically with (p)ppGpp to transform RNA polymerase into a stringent state. The data suggest that pre‐activated SR confers thermotolerance and chaperone independence in part by lowering protein synthesis.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"687 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0