mBio最新文献

{"title":"Insights into the physiological and metabolic features of <i>Thalassobacterium</i>, a novel genus of <i>Verrucomicrobiota</i> with the potential to drive the carbon cycle.","authors":"Xin-Yun Tan, Xin-Jiang Liu, De-Chen Lu, Yu-Qi Ye, Xin-Yu Liu, Fan Yu, Hui Yang, Fan Li, Zong-Jun Du, Meng-Qi Ye","doi":"10.1128/mbio.00305-25","DOIUrl":"10.1128/mbio.00305-25","url":null,"abstract":"<p><p><i>Verrucomicrobiota</i> are widely distributed across various habitats but are difficult to culture. Some previous multiomics analyses reported that <i>Verrucomicrobiota</i> have outstanding metabolic capacity for organic matter degradation and are able to degrade and synthesize polysaccharides, two activities that could contribute significantly to the Earth's carbon cycle. Here, we isolated from marine sediment two novel strains, <i>Thalassobacterium maritimum</i> SDUM461003^T and <i>Thalassobacterium sedimentorum</i> SDUM461004^T, that represent a new genus of the difficult-to-culture phylum <i>Verrucomicrobiota</i>. Genome analysis, functional annotation, and experimental verification revealed that these two strains degrade polysaccharides and antibiotics, including some complex sulfated polysaccharides (SPs), primarily fucoidan and chondroitin sulfate. Moreover, electron microscopy images revealed that these bacteria can synthesize and store large amounts of glycogen. These polysaccharide degradation and synthesis capacities also exist but differ under nitrogen-deficient conditions, indicating that <i>Verrucomicrobiota</i> may have the potential to maintain their normal metabolism by nitrogen fixation under aerobic conditions. Given that polysaccharides and their degradation products are particularly crucial carbon sources for marine microorganisms, <i>Verrucomicrobiota</i> are thought to be important contributors to biogeochemical cycling in the ocean.</p><p><strong>Importance: </strong><i>Verrucomicrobiota</i> are widely distributed and able to utilize a variety of difficult-to-biodegrade polysaccharides, which have a significant impact on the marine carbon cycle. However, there are not enough pure culture strains of <i>Verrucomicrobiota</i>, as hard-to-cultivate bacteria, for us to study. Here, our study reports a new genus in the phylum <i>Verrucomicrobiota</i> and investigates their ability to degrade and synthesize a variety of polysaccharides as well as the mechanism of utilizing difficult-to-degrade polysaccharides. We also explored their special performance on carbon utilization in marine nitrogen-deficient environments. This contributes to deepening our understanding of the involvement of marine microorganisms in the marine carbon cycle.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0030525"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663937","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":"Adaptive evolution of <i>Candida albicans</i> through modulating TOR signaling.","authors":"Yaling Zhang, Lianjuan Yang, Youzhi Zhao, Kang Xiong, Hao Cui, Tianxu Wang, Xiaoping Liu, Chang Su, Yang Lu","doi":"10.1128/mbio.03947-24","DOIUrl":"10.1128/mbio.03947-24","url":null,"abstract":"<p><p><i>Candida albicans</i> stably colonizes humans but is a major fungal pathogen that occupies a wide range of divergent niches within the host. Rapid and effective adaptation to dynamic and contrasting host niches is associated with its pathogenicity. Recent studies have focused on genome evolution implicated in adaptive processes. Here, we demonstrate that modulation of TOR signaling is a mechanism underlying adaptive evolution in <i>C. albicans</i>. Clinical isolates of <i>C. albicans</i> exhibited enhanced commensal fitness in competition with the lab reference strain SC5314, which could be attributed to the diminished GlcNAc-responsive hypha-associated transcription in the gut. <i>In vitro</i> passaging of clinical isolates confers a reduction in TOR signaling, which is detrimental to fitness attributes in evolved strains, including stress response, antifungal drug tolerance, as well as <i>in vivo</i> commensal fitness and invasive infection. This phenomenon is observed independent of strain background and passaging environment. Importantly, inhibition of TOR signaling by rapamycin suppresses the fitness advantage observed in clinical isolates relative to their <i>in vitro</i> passaged derivatives. Thus, <i>C. albicans</i> undergoes rapid evolution via modulating TOR signaling that enables this fungus to adapt to diverse host niches.</p><p><strong>Importance: </strong>Pathogens must be proficient at adapting to their surroundings to survive in the face of a changing microenvironment in the host and cause disease. This is particularly important for commensal-pathogenic organisms such as <i>C. albicans</i> as this fungus colonizes and infects mammalian hosts. Previous studies have focused on genome evolution such as aneuploidies, accumulation of point mutations, or loss of heterozygosity. Here, we demonstrate that <i>C. albicans</i> undergoes rapid adaptive evolution via modulating the TOR pathway. Alterations in TOR activity underlie some evolved traits with important consequences for both host adaptation and pathogenicity in <i>C. albicans</i>. Such mechanisms of adaptive evolution may be exploited by other organisms.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0394724"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542528","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":"CsrA-mediated regulation of a virulence switch in <i>Acinetobacter baumannii</i>.","authors":"Raja Singh, María Pérez-Varela, Jennifer M Colquhoun, Carsten Kröger, Fergal J Hamrock, Ali Shaibah, Ellen L Neidle, Philip N Rather","doi":"10.1128/mbio.04058-24","DOIUrl":"10.1128/mbio.04058-24","url":null,"abstract":"<p><p>CsrA is an RNA binding protein that functions as a global regulator in bacteria. We demonstrate that, in <i>Acinetobacter baumannii</i>, CsrA acts as a positive regulator of the switch from virulent (VIR-O) to avirulent (AV-T) subpopulations. This regulation is mediated, in part, by CsrA interfering with Rho-dependent termination in the mRNA leader region of the <i>ABUW_1645</i> gene, encoding the primary TetR-type transcriptional regulator that drives cells from the VIR-O to the AV-T state. We demonstrate that CsrA directly binds to the <i>ABUW_1645</i> mRNA leader region and interferes with Rho binding. We identify three small RNAs (sRNAs) designated CsrB, CsrC, and CsrD that bind to CsrA and inhibit its activity. Individual overexpression of each sRNA greatly decreased the rate of VIR-O to AV-T switching. Individual deletions of each sRNA increased the frequency of VIR-O to AV-T switching, with loss of CsrB giving the highest increase at 2.4-fold. The expression of each sRNA was strongly dependent on the GacA response regulator and the expression of each sRNA was higher in VIR-O cells than in AV-T variants. This regulation provides a mechanism for the differential control of CsrA activity between VIR-O and AV-T variants.</p><p><strong>Importance: </strong>The World Health Organization has ranked <i>Acinetobacter baumannii</i> atop its \"priority pathogens\" list highlighting the urgent need for new therapeutics against this pathogen. Many <i>A. baumannii</i> strains including AB5075 can rapidly switch between cell subpopulations that are virulent or avirulent. In this study, we identify the RNA binding protein CsrA as an important regulator of this switch. Since this switch represents an \"Achilles Heel\" for pathogenesis, our work may shed light on new mechanisms to lock cells into the avirulent state to block disease.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0405824"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492462","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":"Essential genes encoded by the mating-type locus of the human fungal pathogen <i>Cryptococcus neoformans</i>.","authors":"Zhuyun Bian, Ziyan Xu, Anushka Peer, Yeseul Choi, Shelby J Priest, Konstantina Akritidou, Ananya Dasgupta, Tim A Dahlmann, Ulrich Kück, Minou Nowrousian, Matthew S Sachs, Sheng Sun, Joseph Heitman","doi":"10.1128/mbio.00223-25","DOIUrl":"10.1128/mbio.00223-25","url":null,"abstract":"<p><p>Fungal sexual reproduction is controlled by the mating-type (<i>MAT</i>) locus. In contrast to a majority of species in the phylum Basidiomycota that have tetrapolar mating-type systems, the opportunistic human pathogen <i>Cryptococcus neoformans</i> employs a bipolar mating-type system, with two mating types (<b>a</b> and α) determined by a single <i>MAT</i> locus that is unusually large (~120 kb) and contains more than 20 genes. While several <i>MAT</i> genes are associated with mating and sexual development, others control conserved cellular processes (e.g., cargo transport and protein synthesis), of which five (<i>MYO2</i>, <i>PRT1</i>, <i>RPL22</i>, <i>RPL39</i>, and <i>RPO41</i>) have been hypothesized to be essential. In this study, through genetic analysis involving sporulation of heterozygous diploid deletion mutants, as well as in some cases construction and analyses of conditional expression alleles of these genes, we confirmed that with the exception of <i>MYO2</i>, both alleles of the other four <i>MAT</i> genes are indeed essential for cell viability. We further showed that while <i>MYO2</i> is not essential, its function is critical for infectious spore production, faithful cytokinesis, adaptation for growth at high temperature, and pathogenicity <i>in vivo</i>. Our results demonstrate the presence of essential genes in the <i>MAT</i> locus that are divergent between cells of opposite mating types. We discuss possible mechanisms to maintain functional alleles of these essential genes in a rapidly evolving genomic region in the context of fungal sexual reproduction and mating-type evolution.IMPORTANCESexual reproduction is essential for long-term evolutionary success. Fungal cell-type identity is governed by the <i>MAT</i> locus, which is typically rapidly evolving and highly divergent between different mating types. In this study, we show that the <b>a</b> and α alleles of four genes encoded in the <i>MAT</i> locus of the opportunistic human fungal pathogen <i>C. neoformans</i> are essential. We demonstrate that a fifth gene, <i>MYO2</i>, which had been predicted to be essential, is in fact dispensable for cell viability. However, a functional <i>MYO2</i> allele is important for cytokinesis and fungal pathogenicity. Our study highlights the need for careful genetic analyses in determining essential genes, which is complementary to high-throughput approaches. Additionally, the presence of essential genes in the <i>MAT</i> locus of <i>C. neoformans</i> provides insights into the function, maintenance, and evolution of these fast-evolving genomic regions.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0022325"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492640","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":"Investigation of the <i>Cyanothece</i> nitrogenase cluster in <i>Synechocystis</i>: a blueprint for engineering nitrogen-fixing photoautotrophs.","authors":"Deng Liu, Anindita Bandyopadhyay, Michelle Liberton, Himadri B Pakrasi, Maitrayee Bhattacharyya-Pakrasi","doi":"10.1128/mbio.04052-24","DOIUrl":"10.1128/mbio.04052-24","url":null,"abstract":"<p><p>The nitrogenase gene cluster of unicellular diazotrophic cyanobacteria, such as <i>Cyanothece</i>, is frequently selected by nature for nitrogen-fixing partnerships with eukaryotic phototrophs. The essential cluster components that confer an advantage in such partnerships remain underexplored. To use this cluster for the development of synthetic, phototrophic nitrogen-fixing systems, a thorough and systematic analysis of its constituent genes is necessary. An initial effort to assess the possibility of engineering this cluster into non-diazotrophic phototrophs led to the generation of a <i>Synechocystis</i> 6803 strain with significant nitrogenase activity. In the current study, a refactoring approach was taken to determine the dispensability of the non-structural genes in the cluster and define a minimal gene set for constructing a functional nitrogenase for phototrophs. Using a bottom-up strategy, the <i>nif</i> genes from <i>Cyanothece</i> 51142 were re-organized to form new operons. The genes were then seamlessly removed to determine their essentiality in the nitrogen fixation process. We demonstrate that besides the structural genes <i>nifHDK</i>, <i>nifBSUENPVZTXW</i>, as well as <i>hesAB</i>, are important for optimal nitrogenase function in a phototroph. We also show that optimal expression of these genes is crucial for efficient nitrogenase activity. Our findings provide a solid foundation for generating synthetic systems that will facilitate solar-powered conversion of atmospheric nitrogen into nitrogen-rich compounds, a stride toward a greener world.IMPORTANCEIntegrating nitrogen fixation genes into various photosynthetic organisms is an exciting strategy for converting atmospheric nitrogen into nitrogen-rich products in a green and energy-efficient way. In order to facilitate this process, it is essential that we understand the fundamentals of the functioning of a prokaryotic nitrogen-fixing machinery in a non-diazotrophic, photoautotrophic cell. This study examines a nitrogenase gene cluster that has been naturally selected on multiple occasions for a nitrogen-fixing partnership by eukaryotic photoautotrophs and provides a basic blueprint for designing a photosynthetic organism with nitrogen-fixing ability.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0405224"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492665","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":"Mefloquine reduces the bacterial membrane fluidity of <i>Acinetobacter baumannii</i> and distorts the bacterial membrane when combined with polymyxin B.","authors":"Nagendran Tharmalingam, Harikrishna Sekar Jayanthan, Jenna Port, Fernanda Cristina Possamai Rossatto, Eleftherios Mylonakis","doi":"10.1128/mbio.04016-24","DOIUrl":"10.1128/mbio.04016-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Acinetobacter baumannii&lt;/i&gt; is a high-priority organism for the development of new antibacterial treatments. We found that the antimalarial medication mefloquine (MFQ) permeabilized the bacterial cell membrane of &lt;i&gt;A. baumannii&lt;/i&gt;, decreased membrane fluidity, and caused physical injury to the membrane. MFQ also maintained activity across different pH conditions (pH range: 5-8). Structure-activity relationship analysis using MFQ analogs demonstrated that piperidin-2-yl methanol is required for antibacterial activity. Scanning and transmission electron microscopy demonstrated the compromised morphological and membrane integrity in MFQ-treated cells. MFQ synergized with the membrane permeabilizers polymyxin B and colistin and the MFQ + polymyxin B combination killed bacterial cells more effectively than either treatment alone. MFQ + polymyxin B was effective against other gram-negative bacteria including &lt;i&gt;Escherichia coli&lt;/i&gt;, &lt;i&gt;Burkholderia pseudomallei&lt;/i&gt;, &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt;, and &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt;. Bodipy-cadaverine displacement assays confirmed the active interaction of MFQ with other membrane lipid components, such as lipopolysaccharide, lipid A, lipoteichoic acids, and fatty acids. In all-atom molecular dynamics simulations, lipid interactions facilitated the permeation of MFQ into the simulated Gram-negative membrane. Additionally, positively charged nitrogen in the piperidine group of MFQ seems to enhance interactions with the negatively charged components of the bacterial membrane. MFQ + polymyxin B caused significantly greater curvature in the simulated membrane, indicating greater damage than standalone drug treatment. Finally, &lt;i&gt;in vivo&lt;/i&gt; assays showed that MFQ + polymyxin B rescued &lt;i&gt;Galleria mellonella&lt;/i&gt; larvae infected with &lt;i&gt;A. baumannii&lt;/i&gt;. In conclusion, membrane-active agents such as MFQ may warrant further investigation as a potential components of gram-negative infection treatment, particularly in combination with polymyxin B.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Antimicrobial resistance is a threat globally, and new treatments are urgently needed to combat the rise of multidrug-resistant bacteria. However, the development of anti-infectives has declined over the last two decades due to regulatory, financial and long-term requirement related challenges. In this study, we examined the membrane interactions of the antiparasitic agent mefloquine (MFQ) in combination with polymyxin B, using both &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in silico&lt;/i&gt; approaches to evaluate their potential efficacy against gram-negative bacterial infections. We investigated the interaction of MFQ with lipid bilayers to understand the mechanism through which antibacterial activity is exerted. The piperidine moiety of MFQ plays a critical role in its interaction with the lipid bilayer and facilitates membrane permeabilization. In contrast, the membrane permeabilizer polymyxin B is associated with significant neurotoxicity and ne","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0401624"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492670","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":"Pyruvate kinase directly generates GTP in glycolysis, supporting growth and contributing to guanosine toxicity.","authors":"Fukang She, Kuanqing Liu, Brent W Anderson, Tippapha Pisithkul, Yanxiu Li, Danny K Fung, Tyler McCue, William Mulhern, Daniel Amador-Noguez, Jue D Wang","doi":"10.1128/mbio.03798-24","DOIUrl":"10.1128/mbio.03798-24","url":null,"abstract":"<p><p>Guanosine triphosphate (GTP) is essential for macromolecular biosynthesis, and its intracellular levels are tightly regulated in bacteria. Loss of the alarmone (p)ppGpp disrupts GTP regulation in <i>Bacillus subtilis</i>, causing cell death in the presence of exogenous guanosine and underscoring the critical importance of GTP homeostasis. To investigate the basis of guanosine toxicity, we performed a genetic selection for spontaneous mutations that suppress this effect, uncovering an unexpected link between GTP synthesis and glycolysis. In particular, we identified suppressor mutations in <i>pyk</i>, which encodes pyruvate kinase, a glycolytic enzyme. Metabolomic analysis revealed that inactivating pyruvate kinase prevents guanosine toxicity by reducing GTP levels. Although traditionally associated with ATP generation via substrate-level phosphorylation, <i>B. subtilis</i> pyruvate kinase <i>in vitro</i> was found to produce GTP and UTP approximately 10 and three times more efficiently than ATP, respectively. This efficient GTP/UTP synthesis extends to <i>Enterococcus faecalis</i> and <i>Listeria monocytogenes</i>, challenging the conventional understanding of pyruvate kinase's primary role in ATP production. These findings support a model in which glycolysis directly contributes to GTP synthesis, fueling energy-demanding processes, such as protein translation. Finally, we observed a synergistic essentiality of the Δ<i>ndk</i> Δ<i>pyk</i> double mutant specifically on glucose, indicating that pyruvate kinase and nucleoside diphosphate kinase are the major contributors to nucleoside triphosphate production and complement each other during glycolysis. Our work highlights the critical role of nucleotide selectivity in pyruvate kinase and its broader implications in cellular physiology.</p><p><strong>Importance: </strong>In this study, we reveal that pyruvate kinase, a key glycolytic enzyme, primarily generates GTP from GDP in <i>Bacillus subtilis</i>, relative to other nucleotide triphosphates, such as ATP. This finding, uncovered through genetic selection for mutants that suppress toxic GTP overaccumulation, challenges the conventional understanding that pyruvate kinase predominantly produces ATP via substrate-level phosphorylation. The substantial role of GTP production by pyruvate kinase suggests a model where glycolysis rapidly and directly supplies GTP as the energy currency to power high GTP-demanding processes such as protein synthesis. Our results underscore the importance of nucleotide selectivity (ATP vs GTP vs UTP) in shaping the physiological state and fate of the cell, prompting further exploration into the mechanisms and broader implications of this selective nucleotide synthesis.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0379824"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492685","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":"Reduced prevalence of phage defense systems in <i>Pseudomonas aeruginosa</i> strains from cystic fibrosis patients.","authors":"Daan F van den Berg, Stan J J Brouns","doi":"10.1128/mbio.03548-24","DOIUrl":"10.1128/mbio.03548-24","url":null,"abstract":"<p><p>Cystic fibrosis is a genetic disorder that affects mucus clearance, particularly of the lungs. As a result, cystic fibrosis patients often experience infections from bacteria, which contribute to the disease progression. <i>Pseudomonas aeruginosa</i> is one of the most common opportunistic pathogens associated with cystic fibrosis. The presence of <i>P. aeruginosa</i> complicates the treatment due to its high antibiotic resistance. Thus, research is ongoing to treat these infections with bacterial viruses instead, known as bacteriophages. Notably, <i>P. aeruginosa</i> clinical strains possess a variety of phage defense mechanisms that may limit the effectiveness of phage therapy. In this study, we compared the defense system repertoire of <i>P. aeruginosa</i> strains isolated from cystic fibrosis patients with those from non-cystic fibrosis patients. Our findings reveal that <i>P. aeruginosa</i> strains isolated from cystic fibrosis patients have fewer phage defense mechanisms per strain than from non-cystic fibrosis patients, suggesting altered phage selection pressures in strains colonizing CF patient lungs.IMPORTANCECystic fibrosis patients often experience chronic <i>Pseudomonas aeruginosa</i> lung infections, which are challenging to treat with antibiotics and contribute to disease progression and eventual respiratory failure. Phage therapy is being explored as an alternative treatment strategy for these infections. However, assessing strain susceptibility to phage treatment is essential for ensuring efficacy. To address this, we investigated whether CF-associated clinical <i>P. aeruginosa</i> strains have a distinct phage defense repertoire compared with those isolated from other lung patients. We observed that CF-associated <i>P. aeruginosa</i> strains have significantly fewer phage defenses, possibly affecting the susceptibility of these strains to phage infection.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0354824"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492687","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":"The physical biogeography of <i>Fusobacterium nucleatum</i> in health and disease.","authors":"John P Connolly, Libusha Kelly","doi":"10.1128/mbio.02989-24","DOIUrl":"10.1128/mbio.02989-24","url":null,"abstract":"<p><p><i>Fusobacterium nucleatum</i> (<i>Fn</i>) is an oral commensal inhabiting the human gingival plaque that is rarely found in the gut. However, in colorectal cancer (CRC), <i>Fn</i> can be isolated from stool samples and detected in metagenomes. We hypothesized that ecological characteristics of the gut are altered by disease, enabling <i>Fn</i> to colonize. Multiple genomically distinct populations of <i>Fn</i> exist, but their ecological preferences are unstudied. We identified six well-separated populations in 133 <i>Fn</i> genomes and used simulated metagenomes to demonstrate sensitive detection of populations in human oral and gut metagenomes. In 9,560 samples from 11 studies, <i>Fn</i> population C2 animalis is elevated in gut metagenomes from CRC and Crohn's disease patients and is observed more frequently in CRC stool samples than in the gingiva. Polymorphum, the most prevalent gingival <i>Fn</i> population, is significantly increased in Crohn's stool samples; this effect was significantly stronger in male hosts than in female. We find polymorphum genomes are enriched for biosynthetic gene clusters and fluoride exporters, while C2 animalis are high in iron transporters. <i>Fn</i> populations thus associate with specific clinical and demographic phenotypes and harbor distinct functional features. Ecological differences in closely related groups of bacteria inform microbiome impacts on human health.</p><p><strong>Importance: </strong><i>Fusobacterium nucleatum</i> is a bacterium normally found in the gingiva. <i>F. nucleatum</i> generally does not colonize the healthy gut, but is observed in approximately a third of colorectal cancer (CRC) patient guts. <i>F. nucleatum</i>'s presence in the gut during CRC has been linked to worse prognosis and increased tumor proliferation. Here, we describe the population structure of <i>F. nucleatum</i> in oral and gut microbiomes. We report substantial diversity in gene carriage among six distinct populations of <i>F. nucleatum</i> and identify population disease and body-site preferences. We find the C2 animalis population is more common in the CRC gut than in the gingiva and is enriched for iron transporters, which support gut colonization in known pathogens. We find that C2 animalis is also enriched in Crohn's disease and type 2 diabetes, suggesting ecological commonalities between the three diseases. Our work shows that closely related bacteria can have different associations with human physiology.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0298924"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586186","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":"The human microbiome-derived antimicrobial lugdunin self-regulates its biosynthesis by a feed-forward mechanism.","authors":"Leonie Reetz, Lukas Schulze, Thales Kronenberger, Khaled A Selim, Timm Schaefle, Taulant Dema, Alexander Zipperer, Jens Mößner, Antti Poso, Stephanie Grond, Andreas Peschel, Bernhard Krismer","doi":"10.1128/mbio.03571-24","DOIUrl":"10.1128/mbio.03571-24","url":null,"abstract":"<p><p>Many human microbiome members inhibit bacterial competitors by production of antimicrobial compounds whose expression needs to be tightly controlled to balance the costs and benefits of compound biosynthesis. The nasal commensal <i>Staphylococcus lugdunensis</i> outcompetes <i>Staphylococcus aureus</i> using the antimicrobial lugdunin. The lugdunin biosynthetic gene cluster (BGC) encodes two potential regulators whose roles have remained unknown. Deletion of the regulator genes <i>lugR</i> or <i>lugJ</i> led to increased lugdunin production and/or immunity. While LugR was found to repress the transcription of the biosynthetic <i>lugRABCTDZ</i> operon, LugJ repressed the <i>lugIEFGH</i> export and immunity genes. Both regulators bound to different inverted repeats in the controlled promoter regions. Notably, both repressors were released from cognate promoters to allow transcription upon addition of exogenous lugdunin. Even minor structural changes disabled lugdunin derivatives to induce expression of its BGC, which is consistent with inferior binding to the predicted LugR and LugJ binding pockets. Thus, lugdunin controls its own biosynthesis through a feed-forward mechanism probably to avoid futile production.IMPORTANCEBiosynthetic gene clusters (BGCs) are usually tightly controlled to avoid production of costly goods at inappropriate time points or unfavorable conditions. However, in most cases, the regulatory signals of these clusters have remained unknown. Frequently, quorum sensing or two-component regulatory systems are involved in BGC expression control. This study elucidates the sophisticated regulation of lugdunin biosynthesis and secretion via two independent regulators, LugR and LugJ. Although belonging to different families of repressors, both directly interact with the antimicrobial lugdunin and thereby enhance biosynthesis and secretion in a feed forward-like mechanism.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0357124"},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657625","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}