Molecular Microbiology最新文献

{"title":"Elucidating the Staphylococcus aureus TSST-1 Regulatory Network as a Response to Vaginal pH.","authors":"Carla S Maduta,Nicholas R Walton,Emily P Barbosa,Erica N DeJong,Karine Dufresne,John K McCormick","doi":"10.1111/mmi.70089","DOIUrl":"https://doi.org/10.1111/mmi.70089","url":null,"abstract":"Menstrual toxic shock syndrome (mTSS) is a life-threatening disease caused by the Staphylococcus aureus superantigen TSST-1. At menstruation, the typical acidic vaginal environment rises to near neutral pH, which allows for enhanced TSST-1 production. However, the regulatory network which alters toxin production in response to pH is unknown, despite the importance of this cue in the vaginal environment. To mimic the vaginal environment, we used Vaginally Defined Medium to assess TSST-1 promoter activity in the mTSS strain S. aureus MN8 and discovered a significant upregulation of tst expression occurring at pH 4.5 in a low glucose environment, referred to here as the acidic virulence surge. This increased expression was observed in several regulatory mutant backgrounds tested, including in the absence of SaeS, which has previously been thought to be required for TSST-1 production. Recent studies in non-mTSS S. aureus strains have identified GraXRS as a pH sensor, in addition to its function in cationic antimicrobial peptide sensing. We therefore hypothesized that GraXRS alters TSST-1 expression at low pH. Deletion of the sensor-kinase graS gene resulted in the loss of TSST-1 surge at pH 4.5, indicating that GraXRS is required for the acidic virulence surge. We also found expression from the SaeRS P1 and SarA promoters to be significantly attenuated in the ∆graS background. At low pH, the absence of GraS resulted in reduced T cell activation from S. aureus supernatants when compared to other regulatory mutants, suggesting that GraXRS is the dominant activator at pH 4.5. Finally, we developed an in vivo murine model to measure tst expression using luciferase expression. Our results demonstrate a complex sequence of events that occur in response to changes in pH and further suggests that GraXRS is the main activator of TSST-1 expression at low pH.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"42 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400706","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}

{"title":"Naturally Occurring CodY Variants Alter Ligand Binding, DNA Target Affinity, and Virulence in Clostridioides difficile.","authors":"Md Kamrul Hasan, Sourav Roy, Revathi Govind","doi":"10.1111/mmi.70081","DOIUrl":"10.1111/mmi.70081","url":null,"abstract":"<p><p>Clostridioides difficile is an important nosocomial pathogen and is the major cause of antibiotic-associated diarrhea and colitis. CodY is a global transcriptional regulator that coordinates metabolism and virulence in Gram-positive pathogens by sensing branched-chain amino acids and GTP. In C. difficile, CodY represses toxin production by inhibiting transcription of tcdR and by influencing c-di-GMP turnover. Here, we characterized two naturally occurring CodY variants, CodY(Y146N) and CodY(V58A), whose substitutions lie near the GTP- and ILV-binding sites, respectively. GTP-binding by CodY(Y146N) was severely compromised, while leucine binding was enhanced; CodY(V58A) showed reduced leucine binding. Both variants exhibited reduced ligand-dependent binding to the tcdR promoter and failed to repress toxin production as effectively as CodY(WT). Expression of virulence-associated genes (tcdR, pdcB) was elevated in strains producing either variant. In a hamster infection model, both variant-producing strains were significantly more virulent than the CodY(WT) strain. These findings demonstrate that single amino acid substitutions in this global regulator can alter ligand affinity and promoter binding, potentially rewiring gene regulatory networks to enhance the pathogenic potential of C. difficile.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"98-110"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150156","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}

{"title":"Riboflavin Salvage Supports Glycolysis in Borrelia burgdorferi Through Flavin‐Dependent NAD + Regeneration","authors":"Anna M. Schulz, Grace E. Easterling, Aaditya Balasubramaniyan, Mollie W. Jewett","doi":"10.1111/mmi.70090","DOIUrl":"https://doi.org/10.1111/mmi.70090","url":null,"abstract":"<jats:styled-content style=\"fixed-case\"> <jats:italic>Borrelia burgdorferi</jats:italic> </jats:styled-content> ( <jats:italic>Bb</jats:italic> ), the etiological agent of Lyme disease, lacks the genes for de novo riboflavin biosynthesis and depends on host‐derived riboflavin to generate flavin cofactors FMN and FAD. Riboflavin salvage by <jats:italic>Bb</jats:italic> has demonstrated importance to infection and metabolic homeostasis, though the critical roles of flavin cofactors to central metabolism are not well defined. Here, we demonstrate that riboflavin availability directly controls glycolytic flux through regulation of intracellular redox balance. Disruption of riboflavin uptake by deletion of gene <jats:italic>bb0318</jats:italic> encoding the putative ATPase component of the riboflavin transporter resulted in impaired glycolysis as indicated by reduced intracellular pyruvate and a perturbed NADH/NAD <jats:sup>+</jats:sup> ratio driven by faulty NAD <jats:sup>+</jats:sup> regeneration. We identified coenzyme A disulfide reductase (CoADR) as a key flavin‐dependent mediator of glycolytic flux. A Δ <jats:italic>cdr</jats:italic> mutant mimicked the glycolytic dysregulation of the Δ <jats:italic>bb0318</jats:italic> mutant, but was not rescued by exogenous riboflavin, placing <jats:italic>Bb</jats:italic> CoADR downstream of riboflavin salvage. Biochemical analyses of recombinant <jats:italic>Bb</jats:italic> CoADR demonstrated FAD‐dependent NADH oxidase activity. Targeted mutagenesis of predicted FAD‐binding residues impaired cofactor binding and NADH oxidase activity, further confirming the dependence of <jats:italic>Bb</jats:italic> CoADR on FAD. Together, this work reveals a direct link between riboflavin acquisition and core metabolic processes driven by <jats:italic>Bb</jats:italic> CoADR‐mediated flavin‐dependent redox metabolism.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"31 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355742","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}

{"title":"Mitochondrial Localization and Abundance of Leishmania Cytochrome c Oxidase Subunit IV Is Maintained Following Loss of Mitochondrial Membrane Potential Associated With Mammalian Temperature.","authors":"Isabel Stephany-Brassesco, Edward J Wojcik, Justin C Smith, Ben L Kelly","doi":"10.1111/mmi.70077","DOIUrl":"10.1111/mmi.70077","url":null,"abstract":"<p><p>In eukaryotes, exposure to elevated temperature can disrupt cellular activities, including mitochondrial membrane potential (ΔΨm). Among multiple impacts, loss of ΔΨm typically results in mislocalization of nuclear-encoded mitochondria-destined proteins followed by their proteostatic degradation. As part of their natural transmission cycle, Leishmania encounter an abrupt temperature increase when inoculated into mammalian hosts via the bite of phlebotomine sandflies. How Leishmania maintain mitochondrial protein import in the face of this heat stress remains unknown. We therefore examined the relationship between ΔΨm, abundance of L. major cytochrome c oxidase complex subunit IV (LmCOX4) and its cellular localization functions at insect and mammalian temperatures. Intriguingly, LmCOX4 contains both a mitochondrial targeting sequence (MTS ^LmCOX4) and a PTS-1 glycosomal targeting motif. LmCOX4 is transiently down-modulated following exposure to mammalian temperature, suggesting that heat-induced loss of ΔΨm could lead to LmCOX4 mislocalization and degradation. We find, however, that while transient down-modulation of LmCOX4 promotes viability at mammalian temperature, the associated loss of ΔΨm impacts neither MTS^LmCOX4-mediated localization nor LmCOX4 abundance. Unexpectedly, the canonical positive charges of MTS^LmCOX4 are dispensable for mitochondrial localization. Further, LmCOX4's glycosomal targeting sequence has no apparent role in cellular localization at insect or mammalian temperatures.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"24-43"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868997","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}

{"title":"The Complexity of erm-Mediated Resistance: Structural and Functional Perspectives From β-Hemolytic Streptococci.","authors":"Lillie M Powell, Rita Berisio, P Rocco LaSala, Slawomir Lukomski","doi":"10.1111/mmi.70078","DOIUrl":"10.1111/mmi.70078","url":null,"abstract":"<p><p>Macrolide overuse and resulting resistance crippled the applicability of one of the most important and successful classes of antibiotics. The rising incidence of invasive infections caused by β-hemolytic group A and group B streptococci have been paralleled with marked increases in erythromycin and clindamycin resistance. As a result, resistant invasive group A and group B Streptococcus infections have been classified by the CDC as a concerning level threat since 2019. Acquisition of erythromycin resistance methylase (erm) genes is a major contributor of the MLS_B [macrolide (i.e., erythromycin), lincosamide (i.e., clindamycin), and streptogramin B] resistance phenotype in US isolates. The erm-encoded enzymes utilize the methyl-group from S-adenosyl-L-methionine (SAM) to methylate the adenosine A2058 residue of bacterial ribosomal RNA, which serves as the overlapping rRNA target site for the three MLS_B classes of antibiotics. The major mechanism that regulates Erm methyltransferase production is translational attenuation in the 5' regulatory region upstream of the erm coding sequence. The 5' regulatory region of erm includes at least one short leader peptide ermL, with the leader peptide ribosome binding site (SD1), non-translational stem-loop structures, and the erm start codon with its ribosome binding site (SD2). Binding of a macrolide antibiotic to the ribosome causes stalling during translation of the ermL peptide, which disrupts and alters the formation of inhibitory mRNA hairpins in the erm 5' regulatory region, thereby releasing the erm SD2-site from the posterior stem-loop hairpin, thus allowing Erm protein translation. The streptococcal ErmA, ErmB, and ErmT proteins have conserved structures with primary sequence conservation of residues involved in SAM- and rRNA-binding activity, as well as a high-level of structural conservation. However, the observed variation in the erm 5' regulatory region sequences, transcript expression, and ribosome methylation levels associated with these genes and proteins underscore the regulatory complexity of Erm expression. This review aims to present insights into mechanisms of Erm-mediated resistance, trends in streptococcal epidemiology and treatment, and progress in the development of improved MLS_B drugs that effectively block erm-mediated resistance.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"47-59"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942159","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}

{"title":"ISG15 At the Crossroads of Innate Immunity and Host Survival in Response to Typhoid Toxin.","authors":"Camila Valenzuela, Jost Enninga","doi":"10.1111/mmi.70075","DOIUrl":"10.1111/mmi.70075","url":null,"abstract":"<p><p>Typhoid toxin, a genotoxin secreted by typhoidal Salmonella serovars, has been implicated in diverse host responses ranging from DNA damage to cellular senescence. In this Research Highlight, we discuss how recent findings reveal an unexpected link between toxin-induced DNA damage and a noncanonical interferon-like response centered on ISG15. Using transcriptomic profiling and functional infection models, a recent report by Stark and colleagues shows that intoxicated cells mount a type-I interferon-like transcriptional program independent of interferons. Instead, ISG15 is upregulated via a STING-TBK1-dependent pathway, likely triggered by cytosolic DNA sensing following toxin-induced damage. Strikingly, ISG15 acts independently of its canonical ISGylation activity, remaining in its free form to promote host cell survival and antibacterial defense. Importantly, they demonstrate the role of ISG15 as a key regulator of cellular fate under genotoxic stress. This divergence from canonical interferon signaling does not only add a new flavor to our understanding of the STING pathway, it also points to alternatives for therapeutic intervention that bypass broad interferon activation. By promoting both host cell survival and antimicrobial defenses, this pathway may facilitate persistent infection and intracellular niche formation, revealing a nuanced strategy by which Salmonella exploits host responses to support long-term colonization.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"44-46"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942156","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}

{"title":"Regulation of the Yersinia pseudotuberculosis Type III Secretion System by the CpxAR Two-Component System.","authors":"Karen Hug, Erin Mettert, Melissa Estrada Escobar, Cristina Vargas Vazquez, David Balderas, Sarvind Tripathi, Laya Ashley, Patricia J Kiley, Victoria Auerbuch","doi":"10.1111/mmi.70076","DOIUrl":"10.1111/mmi.70076","url":null,"abstract":"<p><p>The type III secretion system (T3SS) is a cell envelope-spanning injectisome found in many Gram-negative pathogens. Expression of the T3SS is controlled by extracellular signals such as cell envelope stress. The CpxAR two-component system negatively regulates the Yersinia pseudotuberculosis Ysc T3SS, although the mechanism remains unclear. As expected, we found that mutants with constitutive CpxR activity (∆cpxA and cpxR^D51E) led to decreased expression of the Ysc T3SS and its master regulator LcrF. CpxR did not bind to the regulatory regions of lcrF, suggesting an indirect mechanism of regulation. Transcriptome analysis showed that 101 genes were upregulated and 77 genes downregulated in both the ∆cpxA and cpxR^D51E strains compared to wildtype, including seven genes known to modulate transcription. Individual deletion of these seven regulatory factors did not identify any single gene responsible for CpxR-dependent repression of LcrF, suggesting that CpxAR may act through multiple pathways to regulate the Ysc T3SS. However, this analysis led us to examine the role of the osmolarity sensing two-component regulatory system OmpR/EnvZ. Deletion of ompR led to an increase in LcrF and T3SS expression. These results suggest more complex regulation of the Ysc T3SS by two-component regulatory systems than previously appreciated.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"81-97"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148016417","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}

{"title":"Mannosylinositol Phosphorylceramide Biosynthesis Is Required for Cell Surface Adaptation to Ethanol Stress in Saccharomyces cerevisiae.","authors":"Saki Sugihara, Reo Susami, Ayano Koga, Shion Ito, Tomoyuki Nakagawa, Motohiro Tani","doi":"10.1111/mmi.70079","DOIUrl":"10.1111/mmi.70079","url":null,"abstract":"<p><p>Saccharomyces cerevisiae exhibits a remarkable ability to tolerate high concentrations of ethanol during fermentation, yet the molecular basis underlying this adaptive trait remains incompletely understood. Here, we identify the biosynthesis of the complex sphingolipid mannosylinositol phosphorylceramide (MIPC) as a key determinant of ethanol tolerance in S. cerevisiae. Cells lacking the MIPC synthases Csg1 and Csh1 exhibited pronounced ethanol hypersensitivity and loss of viability. This defect was associated with impaired maintenance of cell wall integrity under ethanol stress and was further exacerbated by disruption of the Rim101 transcription factor or the cell wall integrity MAP kinase Slt2 pathway. Notably, ethanol exposure triggered Rim101-dependent eisosome remodeling specifically in MIPC-deficient cells, indicating altered plasma membrane organization in response to ethanol stress. Hypersensitivity of MIPC-deficient cells extended to alcohols with different carbon chain lengths, suggesting a broader defect in alcohol-induced cellular stress responses. Consistent with these defects, MIPC-deficient cells showed reduced growth and survival under high-glucose fermentative conditions that promote ethanol production. Together, our findings demonstrate that MIPC biosynthesis supports cell surface adaptation to ethanol stress by maintaining cell wall integrity and regulating plasma membrane organization, providing new insights into ethanol tolerance and its relevance to fermentation performance.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"60-80"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988262","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}

{"title":"In Salmonella Typhimurium, YiiD Modulates cAMP Levels in Lag Phase During Growth on Succinate.","authors":"John A Ciemniecki, Jessica L Will, Jorge C Escalante-Semerena","doi":"10.1111/mmi.70074","DOIUrl":"10.1111/mmi.70074","url":null,"abstract":"<p><p>In Salmonella Typhimurium (S. Typhimurium), yiiD encodes a two-domain protein, with one domain having bona fide malonyl-ACP decarboxylase activity, and the other showing sequence similarity to Gcn5-type acetyltransferases (GNATs). Recent work on this enzyme was motivated by the essentiality of its decarboxylase domain to initiation of fatty acid biosynthesis in a strain devoid of β-ketoacyl-[acyl-carrier-protein, ACP] synthase III (FabH) activity. A function for the putative GNAT domain has not been established. We find that a ∆yiiD strain has an unconventional, slow-growth lag phenotype during growth on succinate that is only weakly dependent on YiiD decarboxylase activity, implicating the putative GNAT domain. The ∆yiiD mutation suppresses the effect of a ∆rpoS mutation that is known to shorten the lag phase during growth on succinate, suggesting the function of the YiiD protein may also be regulatory. Isolation of spontaneous suppressor mutations in a ∆yiiD strain revealed changes in the promoter of cpdA, the gene encoding cyclic-AMP phosphodiesterase. Exogenous addition of cAMP to the medium fully abrogated the ∆yiiD phenotype, and intracellular cAMP measurements revealed that the ∆yiiD strain fails to accumulate cAMP during lag phase, with levels about half of those measured in the wildtype strain. During the lag phase, the ∆yiiD strain was also measured to have increased expression of the adenylate cyclase gene, cyaA, implying that the mechanism altering cAMP levels occurs posttranscriptionally. We conclude YiiD function is necessary for early cAMP accumulation during transitions into some non-phosphotransferase system (non-PTS) growth conditions. We suggest changing the name of the YiiD protein to LcmM (for lipid and carbon metabolism modulator) to encapsulate its roles in S. Typhimurium physiology.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"15-23"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817855","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}

{"title":"The Absence of E. coli Nucleoid-Associated Protein FIS at Low Temperature Leads to an Adaptation Response That Causes a Shift Towards Genome Compaction in Small Rods.","authors":"Pamela G Jones","doi":"10.1111/mmi.70082","DOIUrl":"10.1111/mmi.70082","url":null,"abstract":"<p><p>In contrast to the rod shape at 37°C, the morphology of Escherichia coli cells at temperatures just above the minimum temperature of growth is small rods. A study was initiated to determine the requirement of nucleoid-associated protein FIS for growth and genome compaction in the small rods at low temperature. Growth and nucleoid staining analyses revealed that the fis null mutant displayed decreased growth and initially formed filaments containing decondensed nucleoids at 12°C, indicating that FIS facilitates production of small rods with condensed nucleoids at low temperature. However, characterized by biphasic growth at low temperature, the fis null mutant exhibited increased growth, cell division, and nucleoid condensation following an acclimation phase. Therefore, the absence of FIS with nucleoid decondensation leads to an adaptation mechanism, termed FIS Null Adaptation Response, that causes a shift towards nucleoid condensation resulting in genome compaction in small rods. Furthermore, overproduction of the HsIVU protease suppressed the cold-sensitive phenotypes of the fis null mutant indicating that degradation of a natural substrate of the protease alleviates the requirement of FIS at low temperature. In addition, null mutations of genes encoding natural substrates of HsIVU (exoribonuclease RNAse R, and cell division inhibitor SulA) were identified as extragenic suppressors of the fis null mutation.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"111-125"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163773","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}