Journal of Bacteriology最新文献

{"title":"Mobile genetic elements in <i>Klebsiella pneumoniae</i>.","authors":"Ting Pan, Qingrong Li","doi":"10.1128/jb.00012-25","DOIUrl":"https://doi.org/10.1128/jb.00012-25","url":null,"abstract":"<p><p><i>Klebsiella pneumoniae</i> is a clinically important pathogenic bacteria that poses a serious threat to human health. In particular, the emergence of hypervirulent and multidrug-resistant <i>K. pneumoniae</i> has posed great challenges in clinical anti-infective therapy. In the <i>K. pneumoniae</i> genome, mobile genetic elements (MGEs), such as plasmids, prophages, transposons, and insertion sequences, enhance bacterial viability and adaptation by mediating the horizontal transfer of virulence genes, antibiotic resistance genes, and other adaptive genes. This paper reviews the types and characteristics of the main MGEs in <i>K. pneumoniae</i>, focusing on their effects on bacterial virulence and antibiotic resistance, with the aim of providing clues for developing infection control measures and new antibacterial drugs.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0001225"},"PeriodicalIF":2.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025912","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":"Genome-wide characterization of hypothiocyanite stress response in <i>Escherichia coli</i>.","authors":"Julia D Meredith, Michael J Gray","doi":"10.1128/jb.00524-24","DOIUrl":"https://doi.org/10.1128/jb.00524-24","url":null,"abstract":"<p><p>Oxidative stress is one of the major methods of microbial population control and pathogen clearing by the mammalian immune system. The methods by which bacteria are able to escape damage by host-derived oxidants such as hydrogen peroxide (H₂O₂) and hypochlorous acid (HOCl) have been relatively well described, while other oxidants' effects on bacteria and their genetic responses are not as well understood. Hypothiocyanite/hypothiocyanous acid (OSCN^-/HOSCN) is one such oxidative stress agent. In this study, we used RNA-sequencing to characterize the global transcriptional response of <i>Escherichia coli</i> to treatment with HOSCN and the impact of deletions of the HOSCN resistance proteins RclA (HOSCN reductase), RclB, and RclC on that response. The HOSCN response of <i>E. coli</i> was different from the previously characterized responses of <i>E. coli</i> to other oxidants such as H₂O₂, superoxide, or HOCl and distinct from the reported responses of other bacteria such as <i>Streptococcus pneumoniae</i> and <i>Pseudomonas aeruginosa</i> to HOSCN. Strikingly, deletion of any one of the Rcl proteins had very similar effects on the transcriptional response to HOSCN, indicating that any disruption of HOSCN defense in <i>E. coli</i> results in similar impacts, despite the fact that we do not currently understand the mechanism(s) by which RclB and RclC contribute to that defense.</p><p><strong>Importance: </strong>Understanding how bacteria sense and respond to oxidative stress provides insights into how our bodies interact with the microbial population within us. In this study, we have characterized the genetic response of <i>E. coli</i> to the important immune oxidant hypothiocyanite and investigated the role of <i>rclABC</i> genes in that response.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0052424"},"PeriodicalIF":2.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982064","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":"Exploration and analytical techniques for membrane curvature-sensing proteins in bacteria.","authors":"Takumi Komikawa, Mina Okochi, Masayoshi Tanaka","doi":"10.1128/jb.00482-24","DOIUrl":"10.1128/jb.00482-24","url":null,"abstract":"<p><p>The mechanism by which cells regulate protein localization is an important topic in the field of bacterial biology. In certain instances, the morphology of the biological membrane has been demonstrated to function as a spatial cue for the subcellular localization of proteins. These proteins are capable of sensing membrane curvature and are involved in a number of physiological functions such as cytokinesis and the formation of membrane-bound organelles. This review presents recent advances in the <i>in vitro</i> evaluation of curvature-sensing properties using artificially controlled membranes and purified proteins, as well as microscopic live cell assays. However, these evaluation methodologies often require sophisticated experiments, and the number of identified curvature sensors remains limited. Thus, we present a comprehensive exploration of recently reported curvature-sensing proteins. Subsequently, we summarize the known curvature-sensing proteins in bacteria, in conjunction with the analytical methodologies employed in this field. Finally, future prospects and further requirements in the study of curvature-sensing proteins are discussed.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0048224"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709843","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>Burkholderia cenocepacia</i>-mediated inhibition of <i>Staphylococcus aureus</i> growth and biofilm formation.","authors":"Tiffany J Brandt, Hayden Skaggs, Thomas Hundley, Deborah R Yoder-Himes","doi":"10.1128/jb.00116-23","DOIUrl":"10.1128/jb.00116-23","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> asymptomatically colonizes the nasal cavity and pharynx of up to 60% of the human population and, as an opportunistic pathogen, can breach its normal habitat, resulting in life-threatening infections. <i>S. aureus</i> infections are of additional concern for populations with impaired immune function such as those with cystic fibrosis (CF) or chronic granulomatous disease. Multi-drug resistance is increasingly common in <i>S. aureus</i> infections, creating an urgent need for new antimicrobials or compounds that improve efficacy of currently available antibiotics. <i>S. aureus</i> biofilms, such as those found in the lungs of people with CF and in soft tissue infections, are notoriously recalcitrant to antimicrobial treatment due to the characteristic metabolic differences associated with a sessile mode of growth. In this work, we show that another CF pathogen, <i>Burkholderia cenocepacia</i>, produces one or more secreted compounds that can prevent <i>S. aureus</i> biofilm formation and inhibit existing <i>S. aureus</i> biofilms. The <i>B. cenocepacia</i>-mediated antagonistic activity is restricted to <i>S. aureus</i> species and perhaps some other staphylococci; however, this inhibition does not necessarily extend to other Gram-positive species. This inhibitory activity is due to death of <i>S. aureus</i> through a contact-independent mechanism, potentially mediated through the siderophore pyochelin and perhaps additional compounds. This works paves the way to better understanding of interactions between these two bacterial pathogens.IMPORTANCE<i>Staphylococcus aureus</i> is a major nosocomial pathogen responsible for infecting thousands of people each year. Some strains are becoming increasingly resistant to antimicrobials, and consequently new treatments must be sought. This paper describes the characterization of one or more compounds capable of inhibiting <i>S. aureus</i> biofilm formation and may potentially lead to development of a new therapeutic.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0011623"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709565","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":"DNA repair is essential for <i>Vibrio cholerae</i> growth on thiosulfate-citrate-bile salts-sucrose (TCBS) medium.","authors":"Alex J Wessel, Drew T T Johnson, Christopher M Waters","doi":"10.1128/jb.00004-25","DOIUrl":"10.1128/jb.00004-25","url":null,"abstract":"<p><p>Thiosulfate-citrate-bile salts-sucrose (TCBS) agar is a selective and differential media for the enrichment of pathogenic <i>Vibrios</i>. We observed that an exonuclease VII (<i>exoVII</i>) mutant of <i>Vibrio cholerae</i> failed to grow on TCBS agar, suggesting that DNA repair mutant strains may be hampered for growth in this selective media. Examination of the selective components of TCBS revealed that bile acids were primarily responsible for the toxicity of the <i>exoVII</i> mutant. Suppressor mutations in DNA gyrase restored growth of the <i>exoVII</i> mutants on TCBS, suggesting that TCBS inhibits DNA gyrase similar to the antibiotic ciprofloxacin. To better understand what factors are important for <i>V. cholerae</i> to grow on TCBS, we generated a randomly barcoded TnSeq (RB-TnSeq) library in <i>V. cholerae</i> and have used it to uncover a range of DNA repair mutants that also fail to grow on TCBS agar. The results of this study suggest that TCBS agar causes DNA damage to <i>V. cholerae</i> similarly to the mechanism of action of fluoroquinolones, and overcoming this DNA damage is critical for <i>Vibrio</i> growth on this selective medium.IMPORTANCETCBS is often used to diagnose cholera infection. We found that many mutant <i>V. cholerae</i> strains are attenuated for growth on TCBS agar, meaning they could remain undetected using this culture-dependent method. Hypermutator strains with defects in DNA repair pathways might be especially inhibited by TCBS. In addition, <i>V. cholerae</i> grown successively on TCBS agar develops resistance to ciprofloxacin.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0000425"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709751","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":"Identification of EcpK, a bacterial tyrosine pseudokinase important for exopolysaccharide biosynthesis in <i>Myxococcus xanthus</i>.","authors":"Luca Blöcher, Johannes Schwabe, Timo Glatter, Lotte Søgaard-Andersen","doi":"10.1128/jb.00499-24","DOIUrl":"10.1128/jb.00499-24","url":null,"abstract":"<p><p>Bacteria synthesize chemically diverse capsular and secreted polysaccharides that function in many physiological processes and are widely used in industrial applications. In the ubiquitous Wzx/Wzy-dependent biosynthetic pathways for these polysaccharides, the polysaccharide co-polymerase (PCP) facilitates the polymerization of repeat units in the periplasm, and in Gram-negative bacteria, also polysaccharide translocation across the outer membrane. These PCPs belong to the PCP-2 family, are integral inner membrane proteins with extended periplasmic domains, and functionally depend on alternating between different oligomeric states. The oligomeric state is determined by a cognate cytoplasmic bacterial tyrosine kinase (BYK), which is either part of the PCP or a stand-alone protein. Interestingly, BYK-like proteins, which lack key catalytic residues and/or the phosphorylated Tyr residues, have been described. In <i>Myxococcus xanthu</i>s, the exopolysaccharide (EPS) is synthesized and exported <i>via</i> the Wzx/Wzy-dependent EPS pathway in which EpsV serves as the PCP. Here, we confirm that EpsV lacks the BYK domain. Using phylogenomics, experiments, and computational structural biology, we identify EcpK as important for EPS biosynthesis and show that it structurally resembles canonical BYKs but lacks residues important for catalysis and Tyr phosphorylation. Using proteomic analyses, two-hybrid assays, and structural modeling, we demonstrate that EcpK directly interacts with EpsV. Based on these findings, we suggest that EcpK is a BY pseudokinase and functions as a scaffold, which by direct protein-protein interactions, rather than by Tyr phosphorylation, facilitates EpsV function. EcpK and EpsV homologs are present in other bacteria, suggesting broad conservation of this mechanism and establishing a phosphorylation-independent PCP-2 subfamily.IMPORTANCEBacteria produce a variety of polysaccharides with important biological functions. In Wzx/Wzy-dependent pathways for the biosynthesis of secreted and capsular polysaccharides in Gram-negative bacteria, the polysaccharide co-polymerase (PCP) is a key protein that facilitates repeat unit polymerization and polysaccharide translocation across the outer membrane. PCP function depends on assembly/disassembly cycles that are determined by the phosphorylation/dephosphorylation cycles of an associated bacterial tyrosine kinase (BYK). Here, we identify the BY pseudokinase EcpK as essential for exopolysaccharide biosynthesis in <i>Myxococcus xanthus</i>. Based on experiments and computational structural biology, we suggest that EcpK is a scaffold protein, guiding the assembly/disassembly cycles of the partner PCP <i>via</i> binding/unbinding cycles independently of Tyr phosphorylation/dephosphorylation cycles. We suggest that this novel mechanism is broadly conserved.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0049924"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604928","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":"A geranylgeranyl reductase homolog required for cholesterol production in Myxococcota.","authors":"Alysha K Lee, Paula V Welander","doi":"10.1128/jb.00495-24","DOIUrl":"10.1128/jb.00495-24","url":null,"abstract":"<p><p>Myxococcota is a phylum of sterol-producing bacteria. They exhibit a clade depth for sterol biosynthesis unparalleled in the bacterial domain and produce sterols of a biosynthetic complexity that rivals eukaryotes. Additionally, the sterol biosynthesis pathways found in this phylum have been proposed as a potential source for sterol biosynthesis in the last eukaryotic common ancestor, lending evolutionary importance to our understanding of this pathway in Myxococcota. However, sterol production has only been characterized in a few species, and outstanding questions about the evolutionary history of this pathway remain. Here, we identify two myxobacteria, <i>Minicystis rosea</i> and <i>Sandaracinus amylolyticus</i>, capable of cholesterol biosynthesis. These two myxobacteria possess a cholesterol biosynthesis pathway that differs in both the ordering and enzymes involved in biosynthesis compared with <i>Enhygromyxa salina</i>, a myxobacterium previously demonstrated to produce cholesterol, as well as the canonical pathways found in eukaryotes. We characterize an alternative bacterial reductase responsible for performing C-24 reduction, further delineating bacterial cholesterol production from eukaryotes. Finally, we examine the distribution and phylogenetic relationships of sterol biosynthesis proteins across both cultured and uncultured Myxococcota species, providing evidence for multiple acquisition events and instances of both horizontal and vertical transfer at the family level. Altogether, this work further demonstrates the capacity of myxobacteria to synthesize eukaryotic sterols but with an underlying diversity in the biochemical reactions that govern sterol synthesis, suggesting a complex evolutionary history and refining our understanding of how myxobacterial cholesterol production relates to their eukaryotic counterparts.</p><p><strong>Importance: </strong>Sterols are essential and ubiquitous lipids in eukaryotes, but their significance in bacteria is less understood. Sterol production in Myxococcota, a phylum of developmentally complex predatory bacteria, has provided insight into novel sterol biochemistry and prompted discussion regarding the evolution of this pathway within both the eukaryotic and bacterial domains. Here, we characterize cholesterol biosynthesis in two myxobacteria, providing evidence for distinct pathway organization and identifying a unique protein responsible for C-24 reduction. We couple these results with the phylogenomic analysis of sterol biosynthesis within Myxococcota, revealing a complicated evolutionary history marked by vertical and horizontal transfer. This suggests a mosaic acquisition of this pathway in Myxococcota and highlights the complex role myxobacteria may have had in sterol transfer to eukaryotes.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0049524"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604926","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":"A call for the United States to continue investing in science.","authors":"Ira Blader, Felicia Goodrum, Michael J Imperiale, Arturo Casadevall, Cesar A Arias, Andreas Baumler, Carey-Ann D Burnham, Christina A Cuomo, Corrella S Detweiler, Graeme N Forrest, Jack A Gilbert, Susan Lovett, Stanley Maloy, Alexander McAdam, Irene Newton, Gemma Reguera, George A O'Toole, Patrick D Schloss, Ashley Shade, Marvin Whiteley","doi":"10.1128/jb.00072-25","DOIUrl":"10.1128/jb.00072-25","url":null,"abstract":"","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0007225"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515568","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":"Identification of a novel phage depolymerase against ST11 K64 carbapenem-resistant <i>Klebsiella pneumoniae</i> and its therapeutic potential.","authors":"Peini Yang, Bin Shan, Xing Hu, Li Xue, Guibo Song, Pingan He, Xu Yang","doi":"10.1128/jb.00387-24","DOIUrl":"10.1128/jb.00387-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Carbapenem-resistant &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; (CRKP) is a clinical pathogen with a high mortality rate, and its clinical management and infection control have become a serious challenge. Phage-encoded depolymerase cleaves the capsular polysaccharide, a major virulence factor of &lt;i&gt;K. pneumoniae&lt;/i&gt;. This study aimed to identify a phage depolymerase targeting ST11 K64 CRKP, evaluate its antimicrobial activity and therapeutic efficacy, and provide new alternative therapeutic strategies for K64 CRKP. Phages were screened from untreated hospital sewage using clinically isolated CRKP as the host bacterium. The host range, efficiency of plaque formation, optimal multiplicity of infection, adsorption efficiency, and one-step growth curve of phage vB_KpnP_IME1309 were determined by the double-layer agar plate culture method. The morphology of the phage was observed by transmission electron microscopy. Phage nucleic acids were extracted for whole-genome sequencing, and the phage-encoded depolymerase gene ORF37 was amplified by polymerase chain reaction. Next, a recombinant plasmid was constructed to induce depolymerase expression, which was verified using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. &lt;i&gt;In vitro&lt;/i&gt; bactericidal activity was determined using a combined serum assay, and the anti-&lt;i&gt;K&lt;/i&gt;. &lt;i&gt;pneumoniae&lt;/i&gt; biofilm effect of depolymerase was determined by crystal violet staining. Finally, a &lt;i&gt;Galleria mellonella&lt;/i&gt; larvae infection model was established to investigate the therapeutic effect of depolymerase on larvae &lt;i&gt;in vivo&lt;/i&gt;. Here, we isolated and characterized a phage vB_KpnP_IME1309 targeting ST11 K64 CRKP, which featured a latent period of 20 min and a burst size of approximately 290 plaque-forming units/cell. It contained 41 predicted open reading frames, of which ORF37 encoded depolymerase. The expressed and purified depolymerase Dep37 cleaved only ST11 K64 CRKP and formed a translucent halo on the agar plate. Dep37 increased the susceptibility of &lt;i&gt;K. pneumoniae&lt;/i&gt; B1 to serum killing, inhibited CRKP biofilm formation, and degraded mature biofilms. The combination of Dep37 and kanamycin was significantly more effective in treating CRKP biofilms compared to either Dep37 or kanamycin alone. An injection of Dep37 at 5 min and 2 h after the CRKP infection of &lt;i&gt;Galleria mellonella&lt;/i&gt; larvae increased their survival rates by up to 73% and 53%, respectively. Depolymerase Dep37 may be used as a potential method for capsule typing of &lt;i&gt;K. pneumoniae&lt;/i&gt;, showing great promise for the development of novel alternative therapeutic strategies against ST11 K64 CRKP.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;A novel phage vB_KpnP_IME1309 targeting ST11 K64 carbapenem-resistant &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; (CRKP) was isolated and characterized. The ORF37 encoding depolymerase gene of phage vB_KpnP_IME1309 was successfully expressed and purified. Depolymerase increases the susceptibility of CRKP to serum killing, inhibits ","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0038724"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709844","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":"The <i>Streptococcus pyogenes</i> mannose phosphotransferase system (Man-PTS) influences antimicrobial activity and niche-specific nasopharyngeal infection.","authors":"Amanda C Marple, Blake A Shannon, Aanchal Rishi, Lana Estafanos, Brent D Armstrong, Veronica Guariglia-Oropeza, Stephen W Tuffs, John K McCormick","doi":"10.1128/jb.00492-24","DOIUrl":"10.1128/jb.00492-24","url":null,"abstract":"<p><p><i>Streptococcus pyogenes</i> is a human-adapted pathogen that can cause multiple diseases, including pharyngitis and skin infections. Although this bacterium produces many virulence factors, how <i>S. pyogenes</i> competes with the host microbiota is not well understood. Here, we detected antimicrobial activity from <i>S. pyogenes</i> MGAS8232 that prevented the growth of <i>Micrococcus luteus</i>. This activity was produced when cells were grown in 5% CO₂ in M17 media supplemented with galactose; however, the addition of alternative sugars coupled with genome sequencing experiments revealed that the antimicrobial phenotype was not related to classical bacteriocins. To further determine genes involved in the production of this activity, a transposon mutant library in <i>S. pyogenes</i> MGAS8232 identified the mannose phosphotransferase system (Man-PTS), a major sugar transporter, as important for the antimicrobial phenotype. Loss-of-function transposon mutants linked to the antimicrobial activity were identified to also be involved in alternative sugar utilization, and additionally, the Man-PTS was further identified from an inadvertent secondary mutation in a bacteriocin operon mutant. Sugar utilization in the Man-PTS mutants demonstrated that galactose, mannose, and N-acetylglucosamine utilization was impaired. RNA-seq experiments in high and low glucose concentrations further characterized the Man-PTS as a glucose transporter; however, transcriptional regulators or virulence factors were not affected with the loss of the Man-PTS. Deletion of Man-PTS demonstrated defects in a mouse model of nasopharyngeal infection but not skin infection. This work suggests that the ability of <i>S. pyogenes</i> to utilize alternative sugars presented by glycans may play a role in acute infection and interactions with the endogenous microbial population existing in the nasopharynx.IMPORTANCE<i>Streptococcus pyogenes</i> is responsible for over 500,000 deaths per year primarily due to invasive infections and post-infection sequelae, although the most common manifestations include pharyngitis and impetigo. <i>S. pyogenes</i> can adapt to its environment through alternative sugar metabolism. Here, we identified an antimicrobial phenotype that was not bacteriocin-related but a by-product of alternative sugar metabolism. The mannose phosphotransferase system was involved in the production of the antimicrobial and was also important for <i>S. pyogenes</i> to utilize alternative sugars and establish nasopharyngeal infection but not skin infection. Overall, this study identified potential strategies used by <i>S. pyogenes</i> for interactions with the endogenous microbiota and further elucidated the importance of sugar metabolism in acute upper respiratory tract infection.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0049224"},"PeriodicalIF":2.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709846","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}