mBio最新文献

{"title":"Inorganic polyphosphate and the stringent response coordinately control cell division and cell morphology in <i>Escherichia coli</i>.","authors":"Christopher W Hamm, Michael J Gray","doi":"10.1128/mbio.03511-24","DOIUrl":"10.1128/mbio.03511-24","url":null,"abstract":"<p><p>Bacteria encounter numerous stressors in their constantly changing environments and have evolved many methods to deal with stressors quickly and effectively. One well-known and broadly conserved stress response in bacteria is the stringent response, mediated by the alarmone (p)ppGpp. (p)ppGpp is produced in response to amino acid starvation and other nutrient limitations and stresses and regulates both the activity of proteins and expression of genes. <i>Escherichia coli</i> also makes inorganic polyphosphate (polyP), an ancient molecule evolutionary conserved across most bacteria and other cells, in response to a variety of stress conditions, including amino acid starvation. PolyP can act as an energy and phosphate storage pool, metal chelator, regulatory signal, and chaperone, among other functions. Here we report that <i>E. coli</i> lacking both (p)ppGpp and polyP have a complex phenotype indicating previously unknown overlapping roles for (p)ppGpp and polyP in regulating cell division, cell morphology, and metabolism. Disruption of either (p)ppGpp or polyP synthesis led to the formation of filamentous cells, but simultaneous disruption of both pathways resulted in cells with heterogenous cell morphologies, including highly branched cells, severely mislocalized Z-rings, and cells containing substantial void spaces. These mutants also failed to grow when nutrients were limited, even when amino acids were added. These results provide new insights into the relationship between polyP synthesis and the stringent response in bacteria and point toward their having a joint role in controlling metabolism, cell division, and cell growth.IMPORTANCECell division is a fundamental biological process, and the mechanisms that control it in <i>Escherichia coli</i> have been the subject of intense research scrutiny for many decades. Similarly, both the (p)ppGpp-dependent stringent response and inorganic polyphosphate (polyP) synthesis are well-studied, evolutionarily ancient, and widely conserved pathways in diverse bacteria. Our results indicate that these systems, normally studied as stress-response mechanisms, play a coordinated and novel role in regulating cell division, morphology, and metabolism even under non-stress conditions.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0351124"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 alphavirus determinants of intercellular long extension formation.","authors":"Caroline K Martin, Judy J Wan, Peiqi Yin, Thomas E Morrison, William B Messer, Vanessa Rivera-Amill, Jonathan R Lai, Nina Grau, Félix A Rey, Thérèse Couderc, Marc Lecuit, Margaret Kielian","doi":"10.1128/mbio.01986-24","DOIUrl":"10.1128/mbio.01986-24","url":null,"abstract":"<p><p>The alphavirus chikungunya virus (CHIKV) is a serious human pathogen that can cause large-scale epidemics characterized by fever and joint pain and often resulting in chronic arthritis. Infection by alphaviruses including CHIKV and the closely related Semliki Forest virus (SFV) can induce the formation of filopodia-like intercellular long extensions (ILEs). ILEs emanate from an infected cell, stably attach to a neighboring cell, and mediate cell-to-cell viral transmission that is resistant to neutralizing antibodies. However, our mechanistic understanding of ILE formation is limited, and the potential contribution of ILEs to CHIKV virulence or human CHIKV infection is unknown. Here, we used well-characterized virus mutants and monoclonal antibodies with known epitopes to dissect the virus requirements for ILE formation. Our results showed that both the viral E2 and E1 envelope proteins were required for ILE formation, while viral proteins 6K and transframe, and cytoplasmic nucleocapsid formation were dispensable. A subset of CHIKV monoclonal antibodies reduced ILE formation by masking specific regions particularly on the E2 A domain. Studies of the viral proteins from different CHIKV strains showed that ILE formation is conserved across the four major CHIKV lineages. Sera from convalescent human CHIKV patients inhibited ILE formation in cell culture, providing the first evidence for ILE inhibitory antibody production during human CHIKV infections.IMPORTANCEChikungunya virus (CHIKV) infections can cause severe fever and long-lasting joint pain in humans. CHIKV is disseminated by mosquitoes and is now found world-wide, including in the Americas, Asia, and Africa. In cultured cells, CHIKV can induce the formation of long intercellular extensions that can transmit virus to another cell. However, our understanding of the formation of extensions and their importance in human CHIKV infection is limited. We here identified viral protein requirements for extension formation. We demonstrated that specific monoclonal antibodies against the virus envelope proteins or sera from human CHIKV patients can inhibit extension formation. Our data highlight the importance of evaluation of extension formation in the context of human CHIKV infection.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0198624"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microcephaly protein ANKLE2 promotes Zika virus replication.","authors":"Adam T Fishburn, Cole J Florio, Thomas N Klaessens, Brian Prince, Neil A B Adia, Nicholas J Lopez, Nitin Sai Beesabathuni, Sydney S Becker, Liubov Cherkashchenko, Sophia T Haggard Arcé, Vivian Hoang, Traci N Shiu, R Blake Richardson, Matthew J Evans, Claudia Rückert, Priya S Shah","doi":"10.1128/mbio.02683-24","DOIUrl":"10.1128/mbio.02683-24","url":null,"abstract":"<p><p>Orthoflaviviruses are positive-sense single-stranded RNA viruses that hijack host proteins to promote their own replication. Zika virus (ZIKV) is infamous among orthoflaviviruses for its association with severe congenital birth defects, notably microcephaly. We previously mapped ZIKV-host protein interactions and identified the interaction between ZIKV non-structural protein 4A (NS4A) and host microcephaly protein ankyrin repeat and LEM domain-containing 2 (ANKLE2). Using a fruit fly model, we showed that NS4A induced microcephaly in an ANKLE2-dependent manner. Here, we explore the role of ANKLE2 in ZIKV replication to understand the biological significance of the interaction from a viral perspective. We observe that ANKLE2 localization is drastically shifted to sites of NS4A accumulation during infection and that knockout of ANKLE2 reduces ZIKV replication in multiple human cell lines. This decrease in virus replication is coupled with a moderate increase in innate immune activation. Using microscopy, we observe dysregulated formation of virus-induced endoplasmic reticulum rearrangements in ANKLE2 knockout cells. Knockdown of the ANKLE2 ortholog in <i>Aedes aegypti</i> cells also decreases virus replication, suggesting ANKLE2 is a beneficial replication factor across hosts. Finally, we show that NS4A from four other orthoflaviviruses physically interacts with ANKLE2 and is also beneficial to their replication. Thus, ANKLE2 likely promotes orthoflavivirus replication by regulating membrane rearrangements that serve to accelerate viral genome replication and protect viral dsRNA from immune detection. Taken together with our previous results, our findings indicate that ZIKV and other orthoflaviviruses hijack ANKLE2 for a conserved role in replication, and this drives unique pathogenesis for ZIKV since ANKLE2 has essential roles in developing tissues.IMPORTANCEZIKV is a major concern due to its association with birth defects, including microcephaly. We previously identified a physical interaction between ZIKV NS4A and host microcephaly protein ANKLE2. Mutations in ANKLE2 cause congenital microcephaly, and NS4A induces microcephaly in an ANKLE2-dependent manner. Here, we establish the role of ANKLE2 in ZIKV replication. Depletion of ANKLE2 from cells significantly reduces ZIKV replication and disrupts virus-induced membrane rearrangements. ANKLE2's ability to promote ZIKV replication is conserved in mosquito cells and for other related mosquito-borne orthoflaviviruses. Our data point to an overall model in which ANKLE2 regulates virus-induced membrane rearrangements to accelerate orthoflavivirus replication and avoid immune detection. However, ANKLE2's unique role in ZIKV NS4A-induced microcephaly is a consequence of ZIKV infection of important developing tissues in which ANKLE2 has essential roles.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0268324"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 and characterization of the functional tetrameric UDP-glucose pyrophosphorylase from <i>Klebsiella pneumoniae</i>.","authors":"Isabel Ramón Roth, Pavel Kats, Timm Fiebig, Françoise Routier, Roman Fedorov, Larissa Dirr, Jana I Führing","doi":"10.1128/mbio.02071-24","DOIUrl":"10.1128/mbio.02071-24","url":null,"abstract":"<p><p>In all kingdoms of life, the enzyme uridine diphosphate-glucose pyrophosphorylase (UGP) occupies a central role in metabolism, as its reaction product uridine diphosphate-glucose (UDP-Glc) is involved in various crucial cellular processes. Pathogens, including fungi, parasites, and bacteria, depend on UGP for the synthesis of virulence factors; in particular, various bacterial species utilize UDP-Glc and its derivatives for the synthesis of lipopolysaccharides, capsular polysaccharides, and biofilm exopolysaccharides. UGPs have, therefore, gained attention as anti-bacterial drug target candidates, prompting us to study their structure-function relationships to provide a basis for the rational development of specific inhibitors. UGP function is tied to its oligomeric state, and the majority of bacterial homologs have been described as tetramers encoded by the <i>galU</i> gene. Uniquely, enterobacterial species harbor a second gene, <i>galF</i>, encoding a protein with high homology to UGP, whose function is somewhat controversial. Here, we show that the <i>galF</i> gene of the opportunistic pathogen <i>Klebsiella pneumoniae</i> encodes a dimeric protein that has lost UGP activity, likely due to a combination of active site mutations and an inability to tetramerize, whereas the functional <i>K. pneumoniae</i> UGP, encoded by <i>galU</i>, is an active tetramer. Our AlphaFold-assisted structure-function relationship studies underline that tetramerization is essential for bacterial UGP function and is facilitated by a common mechanism utilizing conserved key residues. Targeting the respective molecular interfaces, which are absent in human UGP, could provide a means of selectively inhibiting the bacterial virulence factor UGP and potentially rendering pathogenic species avirulent.IMPORTANCEThe enzyme uridine diphosphate-glucose pyrophosphorylase (UGP) is important for the virulence of bacterial pathogens and, therefore, a potential drug target. In this study, we identify the gene encoding the functional UGP in <i>Klebsiella pneumoniae</i>, a bacterium notoriously causing severe antibiotic-resistant infections in humans, and reveal structural and functional features that may aid in the development of new antibiotics.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0207124"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an sRNA-mediated conditional knockdown system for <i>Chlamydia trachomatis</i>.","authors":"Janina Ehses, Kevin Wang, Asha Densi, Cuper Ramirez, Ming Tan, Christine Sütterlin","doi":"10.1128/mbio.02545-24","DOIUrl":"10.1128/mbio.02545-24","url":null,"abstract":"<p><p>We describe a new <i>Chlamydia trachomatis</i> protein depletion method that uses an engineered small RNA (sRNA) to inhibit translation of a target gene. In proof-of-principle experiments, we induced functional knockdown of IncA, a fusion-mediating inclusion membrane protein, as shown with Western blots, loss of IncA staining at the inclusion membrane, and production of multiple chlamydial inclusions within an infected cell. These effects were titratable and reversible. To test for polar effects, we separately targeted the inclusion membrane proteins IncE and IncG, which are expressed from the <i>incDEFG</i> operon. Knockdown of IncE caused loss of IncE and its interacting host protein SNX6 at the inclusion membrane, without affecting IncG protein levels. Similarly, IncG knockdown significantly reduced IncG levels and prevented recruitment of its interacting host protein 14-3-3β, without altering IncE protein levels. These data provide the first genetic evidence that IncE and IncG are necessary for the recruitment of SNX6 and 14-3-3β, respectively, demonstrating the value of this knockdown approach. We also successfully depleted the major chlamydial surface protein, major outer membrane protein (MOMP), which is encoded by a likely essential gene that has not been previously disrupted or knocked down. MOMP knockdown caused severe defects in bacterial morphology and progeny production. Thus, our sRNA-based approach has broad potential as a conditional knockdown method for studying the function of <i>C. trachomatis</i> genes, including essential genes and genes in an operon.IMPORTANCEWe describe a new method to reduce protein levels of a selected gene in the pathogenic bacterium <i>Chlamydia trachomatis</i>. This approach utilizes an engineered small RNA (sRNA) to inhibit translation of the mRNA for a target gene and produced inducible and reversible protein knockdown. Our method successfully knocked down four proteins, including a likely essential gene and individual genes in an operon, without altering protein levels of a neighboring gene. This conditional knockdown method will be useful for studying the function of genes in <i>Chlamydia</i>. It also has the potential to be applied to other obligate intracellular bacteria, including <i>Rickettsia</i> and <i>Coxiella</i>.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0254524"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction between bacterial adhesins leads to coaggregation by the oral bacteria <i>Veillonella parvula</i> and <i>Streptococcus gordonii</i>.","authors":"Jack C Leo","doi":"10.1128/mbio.03279-24","DOIUrl":"10.1128/mbio.03279-24","url":null,"abstract":"<p><p><i>Veillonella parvula</i> is an unusual diderm firmicute that plays a central role in the formation of dental biofilm formation through coaggregation with many other oral bacteria. However, the molecular interactions leading to oral biofilm formation are largely unknown. In a recent study (L. Dorison, N. Béchon, C. Martin-Gallausiaux, S. Chamorro-Rodriguez, et al., mBio 15:e02171-24, 2024, https://doi.org/10.1128/mbio.02171-24), coaggregation by <i>V. parvula</i> was shown to be mediated by trimeric autotransporter adhesins (TAAs), which are large, fibrous surface proteins widespread in Gram-negative bacteria. Importantly, this study identified the binding partner protein on a coaggregating bacterium, <i>Streptococcus gordonii</i>, which the authors called VisA. This finding is the first time a TAA mediating coaggregation with a different type of protein has been established and suggests that specifically interacting protein partners may have coevolved multiple times to allow complex biofilm formation, as exemplified by the development of dental plaque. Understanding these interactions might lead to innovations to reduce build-up of dental plaque and associated oral diseases.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0327924"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2024 Acknowledgment of <i>mBio</i> Reviewers.","authors":"Arturo Casadevall","doi":"10.1128/mbio.03938-24","DOIUrl":"https://doi.org/10.1128/mbio.03938-24","url":null,"abstract":"","PeriodicalId":18315,"journal":{"name":"mBio","volume":"16 2","pages":"e0393824"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a novel <i>covS</i> SNP identified in Australian group A <i>Streptococcus</i> isolates derived from the M1_UK lineage.","authors":"Johanna Richter, Amanda J Cork, Yvette Ong, Nadia Keller, Andrew J Hayes, Mark A Schembri, Amy V Jennison, Mark R Davies, Kate Schroder, Mark J Walker, Stephan Brouwer","doi":"10.1128/mbio.03366-24","DOIUrl":"10.1128/mbio.03366-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Group A &lt;i&gt;Streptococcus&lt;/i&gt; (GAS) is a human-adapted pathogen responsible for a variety of diseases. The GAS M1&lt;sub&gt;UK&lt;/sub&gt; lineage has contributed significantly to the recently reported increases in scarlet fever and invasive infections. However, the basis for its evolutionary success is not yet fully understood. During the transition to systemic disease, the M1 serotype is known to give rise to spontaneous mutations in the control of virulence two-component regulatory system (CovRS) that confer a fitness advantage during invasive infections. Mutations that inactivate CovS function result in the de-repression of key GAS virulence factors such as streptolysin O (SLO), a pore-forming toxin and major trigger of inflammasome/interleukin-1β-dependent inflammation. Conversely, expression of the streptococcal cysteine protease SpeB, which is required during initial stages of colonization and onset of invasive disease, is typically lost in such mutants. In this study, we identified and characterized a novel &lt;i&gt;covS&lt;/i&gt; single nucleotide polymorphism detected in three separate invasive M1&lt;sub&gt;UK&lt;/sub&gt; isolates. The resulting CovS&lt;sup&gt;Ala318Val&lt;/sup&gt; mutation caused a significant upregulation of SLO resulting in increased inflammasome activation in human THP-1 macrophages, indicating an enhanced inflammatory potential. Surprisingly, SpeB production was unaffected. Site-directed mutagenesis was performed to assess the impact of this mutation on virulence and global gene expression. We found that the CovS&lt;sup&gt;Ala318Val&lt;/sup&gt; mutation led to subtle, virulence-specific changes of the CovRS regulon compared to previously characterized &lt;i&gt;covS&lt;/i&gt; mutations, highlighting an unappreciated level of complexity in CovRS-dependent gene regulation. Continued longitudinal surveillance is warranted to determine whether this novel &lt;i&gt;covS&lt;/i&gt; mutation will expand in the M1&lt;sub&gt;UK&lt;/sub&gt; lineage.IMPORTANCEThe M1&lt;sub&gt;UK&lt;/sub&gt; lineage of GAS has contributed to a recent global upsurge in scarlet fever and invasive infections. Understanding how GAS can become more virulent is critical for infection control and identifying new treatment approaches. The two-component CovRS system, comprising the sensor kinase CovS and transcription factor CovR, is a central regulator of GAS virulence genes. In the M1 serotype, &lt;i&gt;covRS&lt;/i&gt; mutations are associated with an invasive phenotype. Such mutations have not been fully characterized in the M1&lt;sub&gt;UK&lt;/sub&gt; lineage. This study identified a novel &lt;i&gt;covS&lt;/i&gt; mutation in invasive Australian M1&lt;sub&gt;UK&lt;/sub&gt; isolates that resulted in a more nuanced virulence gene regulation compared to previously characterized &lt;i&gt;covS&lt;/i&gt; mutations. A representative isolate displayed upregulated SLO production and triggered amplified interleukin-1β secretion in infected human macrophages, indicating an enhanced inflammatory potential. These findings underscore the need for comprehensive analyses of &lt;i&gt;covRS&lt;/i&gt; mutants to fully elucidate their contribu","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0336624"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein <i>S</i>-palmitoylation regulates the virulence of plant pathogenic fungi.","authors":"Mengmeng Guo, Leeza Tariq, Fengming Song","doi":"10.1128/mbio.03472-24","DOIUrl":"10.1128/mbio.03472-24","url":null,"abstract":"<p><p>Protein <i>S</i>-palmitoylation, a universal posttranslational modification catalyzed by a specific group of palmitoyltransferases, plays crucial roles in diverse biological processes across organisms by modulating protein functions. However, its roles in the virulence of plant pathogenic fungi remain underexplored. In a recent study, Y. Duan, P. Li, D. Zhang, L. Wang, et al. (mBio 15:e02704-24, 2024, https://doi.org/10.1128/mbio.02704-24) reported that the palmitoyltransferases UvPfa3 and UvPfa4 regulate the virulence of the rice false smut pathogen <i>Ustilaginoidea virens</i>. Through comprehensive characterization of <i>S</i>-palmitoylation sites, they revealed that <i>S</i>-palmitoylated proteins in <i>U. virens</i> are enriched in mitogen-activated protein (MAP) kinase and autophagy pathways, with MAP kinase UvSlt2 being a key target of UvPfa4-mediated <i>S</i>-palmitoylation. Further investigation demonstrated that <i>S</i>-palmitoylation of UvSlt2 is critical for its kinase activity, substrate interaction ability, and virulence function in <i>U. virens</i>. These findings reveal UvPfa4-mediated <i>S</i>-palmitoylation as a vital regulatory mechanism in <i>U. virens</i> virulence, highlighting the importance of protein <i>S</i>-palmitoylation in the pathogenicity of plant pathogenic fungi.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0347224"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 pneumococcal bacteriocin streptococcin B is produced as part of the early competence cascade and promotes intraspecies competition.","authors":"J D Richardson, Emily Guo, Ryan M Wyllie, Paul Jensen, Suzanne Dawid","doi":"10.1128/mbio.02993-24","DOIUrl":"10.1128/mbio.02993-24","url":null,"abstract":"<p><p><i>Streptococcus pneumoniae</i> is an important human pathogen that normally resides in the human nasopharynx. Competence-mediated bacteriocin expression by <i>S. pneumoniae</i> plays a major role in both the establishment and persistence of colonization on this polymicrobial surface. Over 20 distinct bacteriocin loci have been identified in pneumococcal genomes, but only a small number have been characterized phenotypically. In this work, we demonstrate that three-fourths of <i>S. pneumoniae</i> strains contain a highly conserved <i>scb</i> locus that encodes an active lactococcin 972-like bacteriocin called streptococcin B. In these backgrounds, the <i>scbABC</i> locus is part of the early competence cascade due to a ComE binding site in the promoter region. Streptococcin B producing strains target both members of the population that have failed to activate competence and the 25% of the population that carry a naturally occurring deletion of the ComE binding site and the functional bacteriocin gene. The ComR-type regulator found directly upstream of the <i>scb</i> locus in <i>S. pneumoniae</i> strains can activate <i>scb</i> expression independent of the presence of the ComE binding site but only when stimulated by a peptide that is encoded in the <i>scb</i> locus of <i>Streptococcus pseudopneumoniae</i>, a closely related bacterium that also inhabits the human nasopharynx. Given the co-regulation with competence and the phenotypic confirmation of activity, streptococcin B represents a previously unrecognized fratricide effector that gives producing strains an additional advantage over the naturally occurring deleted strains during colonization.</p><p><strong>Importance: </strong><i>Streptococcus pneumoniae</i> is a common cause of pneumonia, meningitis, sinusitis, and otitis media. In order to successfully colonize humans, a prerequisite to the development of invasive disease, <i>S. pneumoniae</i> must compete with other bacterial inhabitants of the nasal surface for space and nutrients. Bacteriocins are small antimicrobial peptides produced by bacteria that typically target neighboring bacteria by disruption of the cell surface. <i>S. pnuemoniae</i> encodes a large number of potential bacteriocin, but, for most, their role in competitive interactions has not been defined. This work demonstrates that isolates that produce the bacteriocin streptococcin B have an advantage over non-producers. These observations contribute to our understanding of the competitive interactions that precede the development of <i>S. pneumoniae</i> disease.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0299324"},"PeriodicalIF":5.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}