mSystems最新文献

{"title":"Bacterial alarmone (p)ppGpp mediates the pathogenicity of <i>Clavibacter michiganensis</i> via a dual mechanism that affects both enzyme production and the Tat secretion system.","authors":"Xiaoli Xu, Kaihong Bai, Jia Shi, Chengxuan Yu, Shuang Song, Na Jiang, Jianqiang Li, Laixin Luo","doi":"10.1128/msystems.00135-25","DOIUrl":"https://doi.org/10.1128/msystems.00135-25","url":null,"abstract":"<p><p>The gram-positive bacterium <i>Clavibacter michiganensis</i> (Cm) causes bacterial canker of tomato. The infection process of Cm is of considerable interest, and the role of the alarmone guanosine tetraphosphate or pentaphosphate [(p)ppGpp], a global regulator, has been strongly implicated in bacterial survival and pathogenicity. Transcriptome analysis comparing a (p)ppGpp-deficient strain (Δ<i>rel</i>) to the wild-type strain demonstrated that (p)ppGpp down-regulates the expression of many genes encoding ribosomal components and ABC transporter proteins, while up-regulating genes associated with amino acid metabolism, biofilm synthesis, and the production and secretion of cell-wall degrading enzymes. Biochemical assays showed reduced biofilm synthesis and extracellular activity of cell-wall degrading enzymes such as amylase and xylanase. Moreover, the results of microscale thermophoresis and electrophoretic mobility shift assays indicated that (p)ppGpp interacts with the transcription factor Vatr1 to directly suppress expression of the xylanase gene <i>xysB</i>. Meanwhile, amidase reporter assays revealed that xylanase secretion depends on the Tat secretion system, which was significantly inhibited in Δ<i>rel</i>, leading to intracellular accumulation of the xylanase protein. Taken together, these results indicate that (p)ppGpp plays a complex role in the pathogenicity of <i>C. michiganensis</i>, mediating, among other things, not only the production of cell-wall degrading enzymes but also their transport and secretion.</p><p><strong>Importance: </strong>This study reveals the pivotal role of the bacterial alarmone guanosine tetraphosphate and guanosine pentaphosphate in the pathogenicity of <i>Clavibacter michiganensis</i>, a significant plant pathogen. Through the identification of its dual mechanisms in regulating enzyme production and the Tat secretion system, we uncover key insights into bacterial virulence strategies. Our findings not only advance the understanding of bacterial stress response systems but also offer new opportunities for developing targeted interventions to combat plant bacterial diseases, ultimately contributing to agricultural sustainability and food security.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0013525"},"PeriodicalIF":4.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775833","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":"Phylogenetic intermixing reveals stable fly-mediated circulation of mastitis-associated bacteria in dairy settings.","authors":"Andrew J Sommer, Travis K Worley, Panagiotis Sapountzis, Kerri L Coon","doi":"10.1128/msystems.00215-25","DOIUrl":"https://doi.org/10.1128/msystems.00215-25","url":null,"abstract":"<p><p><i>Stomoxys</i> flies are common blood-feeding pests on dairy farms and are suspected carriers of pathogenic bacteria due to their close association with manure and cattle hosts. While prior studies have used amplicon sequencing and culture-dependent methodologies to characterize the composition of the <i>Stomoxys</i> microbiota, little is known about strain-level acquisition of mastitis-causing bacteria from manure by <i>Stomoxys</i> or the functional diversity of <i>Stomoxys</i>-associated taxa. In this study, we address these key knowledge gaps by using whole genome sequencing to provide the first comparative genomic analysis of <i>Stomoxys-</i>derived <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, and <i>Staphylococcaceae</i> isolates. Our results show that fly and manure isolates collected from the same farm system are phylogenetically interspersed, with subsequent pairwise genome alignments revealing near-identical strains and plasmids shared between the two sources. We further identify a phylogenetic clade of <i>Mammaliicoccus sciuri</i> containing known mastitis agents associated with both flies and manure. Functional analysis reveals that this clade is highly enriched in xylose metabolism genes that are rare across other <i>M. sciuri</i> lineages, suggesting potential niche differentiation within the genus. Collectively, our results provide strong evidence for the acquisition of fecal-associated bacteria by adult <i>Stomoxys</i> flies, confirming the link between biting muscid flies and manure habitats. The intermixing of fly and manure isolates in clinically relevant taxonomic groups strongly suggests that flies serve as carriers of opportunistic mastitis-causing or other fecal-borne pathogens and may serve as important vehicles of pathogen dissemination across the dairy farm environment.IMPORTANCEBovine mastitis causes up to $32 billion dollars in losses annually in the global dairy industry. Opportunistic intramammary pathogens can be transmitted through incidental contact with bacteria in environmental reservoirs like manure. However, factors affecting the abundance, persistence, and spread of these bacteria are not well understood. Our research shows that mastitis pathogens are present in the guts of blood-feeding <i>Stomoxys</i> (stable) flies, which develop in cow feces and bite cows. Genomic analysis of isolates from flies, manure, and mastitis cases reveals that strains and antimicrobial resistance genes are shared between these sources. Further analysis of fly gut isolates shows virulence factors and possible niche specialization, identifying fly-associated clades with known mastitis agents from mastitic cows. This strongly suggests that <i>Stomoxys</i> flies play a role in the carriage and circulation of bovine mastitis pathogens from manure in dairy settings.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0021525"},"PeriodicalIF":4.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760499","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":"Elucidating the interplay between metabolites and microorganisms in the spermosphere of common bean (<i>Phaseolus vulgaris</i> L.) seeds.","authors":"Chandrodhay Saccaram, Marie Simonin, Stéphanie Boutet, Céline Brosse, Shuang Peng, Tracy François, Boris Collet, François Perreau, Delphine Sourdeval, Coralie Marais, Matthieu Barret, Loïc Rajjou, Massimiliano Corso","doi":"10.1128/msystems.00707-25","DOIUrl":"https://doi.org/10.1128/msystems.00707-25","url":null,"abstract":"<p><p>The spermosphere, the dynamic interface surrounding germinating seeds, is shaped by the intricate interplay between seed-exuded natural compounds and seed-associated microbial communities. In this work, we provide the first comprehensive metabolomic and microbiome characterization of common bean (<i>Phaseolus vulgaris</i>) spermosphere of eight genotypes produced in two contrasted production regions. Through an integrated approach, we explored the metabolomic and microbiota composition in the spermosphere of germinating common bean seeds and elucidated their environmental and genotype regulation. We detected and analyzed 2,467 metabolite features (Mf) through untargeted metabolomics categorized into fourteen metabolic categories, highlighting the prevalence of amino acids, flavonoids, and terpenoids. Genotype was the key factor influencing the chemical composition of the spermosphere. Furthermore, we identified 19 bacterial families and 23 fungal families inhabiting the spermosphere, with both genotype and seed production location exerting varying degrees of influence on microbial community composition. Through a multiscale integrated approach, we revealed specific associations between metabolites and microorganisms, such as negative correlation between flavonoids and <i>Bacillus</i> spp., emphasizing the genotype-dependent nature of these interactions. This comprehensive investigation sheds light on the mechanisms underlying seed germination and the complex interactions between plant genotypes, seed exudates, environmental conditions, and microbial communities in the spermosphere. These findings provide a framework for developing innovative strategies to promote seed health and sustainable crop production.</p><p><strong>Importance: </strong>The spermosphere, the dynamic interface around germinating seeds, is shaped by the intricate interplay between seed-exuded compounds and microbial communities. Despite the importance of these interactions for eventual seedling emergence and health, little knowledge is available on the subject. We are the first to comprehensively analyze the chemical and microbial diversity of the spermosphere of <i>Phaseolus vulgaris</i> (common bean). We identified thousands of primary and specialized metabolites, highlighting their diversity but largely unknown roles in germinating seed-environment interactions. We revealed significant genotype-driven differences in the chemical composition as well as the influence of both genotype and seed production location on microbial community structure in the spermosphere. Our metabolome-microbiome integrative analysis suggests that common bean shapes the spermosphere microbiome through specific seed exudates. This research advances our understanding of the metabolic capabilities and ecological roles of seed microbiota within the spermosphere, contributing to our understanding of seed health and vigor.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0070725"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753859","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":"Genomic and phenotypic characterization of methicillin-resistant <i>Staphylococcus aureus</i> ST965: an emerging hospital-adapted clone with enhanced invasiveness.","authors":"Jianbo Lv, Zhixuan Chen, Can Yang, Yu Huang, Xinru Yuan, Li Shen, Cailin Wan, Peiyao Zhou, Haojin Gao, Weihua Han, Junhong Shi, Bingjie Wang, Fangyou Yu","doi":"10.1128/msystems.00798-25","DOIUrl":"https://doi.org/10.1128/msystems.00798-25","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> sequence type 965 (ST965) represents a significant member of clonal complex 5. However, there are still significant gaps in research regarding the resistance, virulence, and distribution characteristics of methicillin-resistant <i>S. aureus</i> (MRSA) ST965. Here, we conducted a comprehensive analysis of 27 ST965-MRSA genomes from three different countries, including 20 genomes sequenced in this study and 7 genomes retrieved from public databases. Our results indicate that ST965-MRSA mainly originates from China (92.6%, 25 out of 27) and was first reported in 2013. SCC<i>mec</i> IV typing (75%, 21 out of 27) and <i>spa</i> t062 typing (75%, 21 out of 27) constituted its predominant clonal characteristics. Among ST965-MRSA clinical isolates, bloodstream infection samples accounted for 35%. A novel multidrug-resistant plasmid (pYF965) was identified in ST965-MRSA, which contains <i>erm</i> genes integrated via Tn551 into pTZ2162 and simultaneously contains <i>aac(6')-Ie</i> and <i>blaI-blaR-blaZ</i>. Through the acute pathogenicity model, ST965-MRSA exhibited higher hemolytic activity and mortality rates compared to N315 (ST5), yet their overall virulence remained significantly lower than the highly virulent strain USA300-LAC (ST8) (<i>P <</i> 0.0001). Notably, in terms of persistent infection, the bacterial colonization levels of ST965-MRSA in the heart, lungs, and spleen <i>in vivo</i> were significantly higher than those of N315 (ST5) and USA300-LAC (ST8) (<i>P <</i> 0.05). Particularly, its immune evasion ability and intracellular survival ability were superior to those of ST5 and ST8 (<i>P <</i> 0.05). This study elucidated the biological characteristics of ST965-MRSA for the first time, expanding our understanding of the molecular epidemiology of the ST965 clone.</p><p><strong>Importance: </strong>As an emerging clonal lineage, ST965 has been predominantly discovered in Asian regions. However, research regarding the ST965-MRSA remains highly limited at present. Therefore, we conducted a detailed analysis of the genomic characteristics of ST965-MRSA and, combined with phenotypic experiments, further revealed their potential pathogenic risks. This study initially uncovers the potential global transmission and genetic and phenotypic features of ST965-MRSA and offers valuable insights for controlling and preventing persistent hospital infections.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0079825"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753860","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":"HIV-1 Vpu interacts with RBM10 to promote HIV-1 infection.","authors":"Boye Li, Yanzhe Hao, Xianbin Meng, Xiaoming Wang, Qingyan Li, Runqing Jia, Yishu Yang, Jinning Yang, Boyang Yu, Tian Chen, Wenmei Zhang, Xiaoguang Zhang, Xiayan Wang, Qin Hu","doi":"10.1128/msystems.00403-25","DOIUrl":"https://doi.org/10.1128/msystems.00403-25","url":null,"abstract":"<p><p>Viral protein U (Vpu), an accessory protein of HIV-1, functions by antagonizing or hijacking various host factors to allow the virus to evade host immune surveillance and facilitate viral release. Nevertheless, there is limited understanding regarding the impact of Vpu on the biogenesis of HIV-1 RNAs. In this study, we utilized ascorbate peroxidase 2 (APEX2)-based proximity labeling techniques in combination with mass spectrometry and immunoprecipitation-mass spectrometry (IP-MS) to characterize interactions between HIV-1 Vpu and host proteins. We identified nine cellular targets of Vpu. Among these targets, our research demonstrated the interaction between Vpu and RNA-binding motif protein 10 (RBM10), which results in the degradation of RBM10 through the ubiquitin-proteasome pathway. The expression of RBM10 exerted an inhibitory effect on virus replication by binding to viral RNA and reducing the levels of incompletely spliced HIV-1 transcripts. Additionally, it promoted the transcription of various antiviral genes. The findings elucidate the role of HIV-1 Vpu in RNA replication and identify RBM10 as a novel regulator of HIV-1 transcription.IMPORTANCEA comprehensive analysis utilizing APEX2-MS and IP-MS techniques identified a total of 24 cellular targets of Vpu, three of which have been documented as restriction factors. Vpu-interacting proteins were found to be significantly enriched in pathways related to cell adhesion, RNA transport, and the spliceosome. The identification of RBM10 as a novel regulator of HIV-1 replication and infectivity, and RBM10 regulated transcription of both viral and host RNA transcripts. Vpu interacted with RBM10 and promoted its degradation through the ubiquitin-proteasome pathway.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0040325"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753864","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":"Metagenomic estimation of absolute bacterial biomass in the mammalian gut through host-derived read normalization.","authors":"Gechlang Tang, Alex V Carr, Crystal Perez, Katherine Ramos Sarmiento, Lisa Levy, Johanna W Lampe, Christian Diener, Sean M Gibbons","doi":"10.1128/msystems.00984-25","DOIUrl":"https://doi.org/10.1128/msystems.00984-25","url":null,"abstract":"<p><p>Absolute bacterial biomass estimation in the human gut is crucial for understanding microbiome dynamics and host-microbe interactions. Current methods for quantifying bacterial biomass in stool, such as flow cytometry, quantitative polymerase chain reaction (qPCR), or spike-ins, can be labor-intensive, costly, and confounded by factors like water content, DNA extraction efficiency, PCR inhibitors, and other technical challenges that add bias and noise. We propose a simple, cost-effective approach that circumvents some of these technical challenges: directly estimating bacterial biomass from metagenomes using bacterial-to-host (B:H) read count ratios. We compared B:H ratios to the standard methods outlined above, demonstrating that B:H ratios are useful proxies for bacterial biomass in stool and possibly in other host-associated substrates. B:H ratios in stool were correlated with bacterial-to-diet (B:D) read count ratios, but B:D ratios exhibited a substantial number of outlier points. Host read depletion methods reduced the total number of human reads in a given sample, but B:H ratios were strongly correlated before and after host read depletion, indicating that host read depletion did not reduce the utility of B:H ratios. B:H ratios showed expected variation between health and disease states and were generally stable in healthy individuals over time. Finally, we showed how B:H and B:D ratios can be used to track antibiotic treatment response and recovery. B:H ratios offer a convenient alternative to other absolute biomass quantification methods, without the need for additional measurements, experimental design considerations, or machine learning, enabling robust absolute biomass estimates directly from stool metagenomic data.IMPORTANCEIn this study, we asked whether normalization by host reads alone was sufficient to estimate absolute bacterial biomass directly from stool metagenomic data, without the need for synthetic spike-ins, additional experimental biomass measurements, or training data. The approach assumes that the contribution of host DNA to stool is more constant or stable than biologically relevant fluctuations in bacterial biomass. We find that host read normalization is an effective method for detecting variation in gut bacterial biomass. Absolute bacterial biomass is a key metric that often gets left out of gut microbiome studies, and empowering researchers to include this measure more broadly in their metagenomic analyses should serve to improve our understanding of host-microbiota interactions.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0098425"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753865","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":"Gut microbiota contribute to high-altitude adaptation in tree sparrows.","authors":"Tingbei Bo, Gang Song, Mengru Zhang, Xiaoming Xu, Jundong Duan, Huishang She, Yun Fang, Wenting Li, Jing Wen, Jingsong Liu, Dehua Wang, Fumin Lei","doi":"10.1128/msystems.00630-25","DOIUrl":"https://doi.org/10.1128/msystems.00630-25","url":null,"abstract":"<p><p>The intricate relationship between gut microbiota and various physiological functions in animals has emerged as a focal point in understanding host adaptability. Unlike the native birds of the Qinghai-Tibet Plateau (QTP), the tree sparrow (<i>Passer montanus</i>) is believed to have colonized the plateau within the last few thousand years. Given the vast expanse and harsh conditions of the plateau, the role of gut microbiota in facilitating the tree sparrow's adaptation to this high-altitude habitat remains largely unexplored and holds significant scientific interest. Therefore, we employed a multidisciplinary approach combining amplicon sequencing, transcriptome analysis, and fecal microbiota transplantation (FMT) to investigate the functional role of gut microbiota in high-altitude tree sparrows across different seasons. Results indicate that the gut microbiota of tree sparrows exhibits seasonal and altitude-dependent changes, with an increase in <i>Lactobacillus</i> in winter, which may promote heat production to cope with the cold. FMT experiments confirmed that \"high-altitude gut microbiota\" enhances the expression of heat-related proteins (avUCP) and upregulates heat-related genes <i>syt1</i> and <i>chodl</i>. These findings suggest an adaptive strategy whereby tree sparrows utilize their gut microbiota to modulate energy metabolism, ultimately conserving energy in the resource-limited high-altitude environment.</p><p><strong>Importance: </strong>This study provides one evidence that gut microbiota mediates high-altitude adaptation in tree sparrow. By integrating multi-omics and fecal transplantation in tree sparrows (<i>Passer montanus</i>)-a species invading the Qinghai-Tibet Plateau within millennia-we reveal seasonally dynamic microbial strategies critical for survival in extreme environments. These findings establish gut microbiota as a key driver of rapid altitudinal adaptation, offering new insights into how microbial functions enable vertebrate range expansion into challenging ecosystems. The mechanistic framework also informs conservation strategies for wildlife facing climate-driven habitat shifts.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0063025"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753861","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":"A combination of phenotypic responses and genetic adaptations enables <i>Staphylococcus aureus</i> to withstand inhibitory molecules secreted by <i>Pseudomonas aeruginosa</i>.","authors":"Lukas Schwyter, Selina Niggli, Natalia Zajac, Lucy Poveda, Witold Eryk Wolski, Christian Panse, Ralph Schlapbach, Rolf Kümmerli, Jonas Grossmann","doi":"10.1128/msystems.00262-25","DOIUrl":"https://doi.org/10.1128/msystems.00262-25","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> frequently co-occur in infections, and there is evidence that their interactions can negatively affect disease outcomes. <i>P. aeruginosa</i> is known to be dominant, often compromising <i>S. aureus</i> through the secretion of inhibitory compounds. We previously demonstrated that <i>S. aureus</i> can become resistant to growth-inhibitory compounds during experimental evolution. While resistance arose rapidly, the underlying mechanisms were not obvious as only a few genetic mutations were associated with resistance, while ample phenotypic changes occurred. We thus hypothesize that resistance may result from a combination of phenotypic responses and genetic adaptation. Here, we tested this hypothesis using proteomics. We first focused on an evolved strain that acquired a single mutation in <i>tcyA</i> (encoding a transmembrane transporter unit) upon exposure to <i>P. aeruginosa</i> supernatant. We show that this mutation leads to a complete abolishment of transporter synthesis, which confers moderate protection against <i>Pseudomonas</i> quinolone signal and selenocystine, two toxic compounds produced by <i>P. aeruginosa</i>. However, this genetic effect was minor compared to the fundamental phenotypic changes observed at the proteome level when both ancestral and evolved <i>S. aureus</i> strains were exposed to <i>P. aeruginosa</i> supernatant. Major changes involved the downregulation of virulence factors, metabolic pathways, and membrane transporters, and the upregulation of reactive oxygen species scavengers and an efflux pump. Our results suggest that the observed multivariate phenotypic response is a powerful adaptive strategy, offering instant protection against competitors in fluctuating environments and reducing the need for hard-wired genetic adaptations.IMPORTANCEDifferent bacterial pathogens can co-occur in infections, where they interact with one another and influence disease severity. Previous research showed that pathogens can evolve and adapt to co-infecting species. Here, we show that evolution through genetic mutations and selection is not necessarily required to change pathogen behavior. Instead, we found that the human pathogen <i>Staphylococcus aureus</i> is able to plastically respond to the presence of <i>Pseudomonas aeruginosa</i>, a competing pathogen. Through proteomics and metabolomics, we demonstrate that <i>S. aureus</i> undergoes substantial proteomic alterations in response to <i>P. aeruginosa</i> by downregulating virulence factor expression, changing metabolism, and mounting protective measures against toxic compounds. Our work highlights that pathogens possess sophisticated mechanisms to respond to competitors to secure growth and survival in polymicrobial infections. We predict such plastic responses to have significant impacts on infection outcomes.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0026225"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753858","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":"The diverse phenotypic and mutational landscape induced by fluoroquinolone treatment.","authors":"Sayed Golam Mohiuddin, Pouria Kavousi, Diego Figueroa, Sreyashi Ghosh, Mehmet A Orman","doi":"10.1128/msystems.00713-25","DOIUrl":"https://doi.org/10.1128/msystems.00713-25","url":null,"abstract":"<p><p>Antibiotic resistance remains a major public health challenge, yet the broader effects of antibiotic treatment on bacterial tolerance, resistance, and fitness are not fully understood. In this study, we investigated how <i>Escherichia coli</i> adapts to fluoroquinolone stress using adaptive laboratory evolution. Cell populations were subjected to repeated cycles of high-dose ofloxacin exposure followed by drug-free recovery, a dynamic model that imposes alternating selective pressure and inter-strain competition, reflecting real-world clinical or environmental conditions. Our results demonstrate that tolerance and resistance can evolve independently, even under identical conditions, leading to diverse phenotypic outcomes. Notably, we observed the emergence of mutants with high ofloxacin tolerance but reduced minimum inhibitory concentrations, an outcome that challenges conventional understanding. Fitness traits, including lag phase duration, doubling time, competition score, redox activity, and ATP levels, were variably affected across evolved strains, with no consistent correlation between fitness and tolerance or resistance. Whole-genome sequencing revealed both known and novel mutations, with limited convergence across populations. For example, while mutations in the <i>icd</i> gene were commonly observed, many other mutations, including in <i>cyoE, lgoT, yghC</i>, <i>rnd</i>, <i>dld</i>, and <i>uidB</i>, were unique to individual lineages. The lack of convergence across evolved populations may reflect the influence of competitive dynamics during recovery phases, where differing growth advantages shape selection in parallel with antibiotic pressure. These findings underscore the complexity of microbial adaptation and highlight how fluctuating environments and population-level interactions can drive non-uniform evolutionary outcomes.IMPORTANCEAntibiotic resistance poses a critical global health threat, with antibiotic-tolerant cells further complicating treatment by promoting infection relapse and enabling resistance mutations. Though tolerant cells can evolve into resistant strains, their phenotypic and genotypic characteristics are still poorly understood. In this study, we used adaptive laboratory evolution to generate several distinct ofloxacin-resistant mutants and examined their fitness (e.g., lag phase), metabolic traits (e.g., ATP levels), and genetic adaptations through whole-genome sequencing. We uncovered novel findings, including highly tolerant mutants exhibiting unexpectedly low minimum inhibitory concentrations and others with shorter lag phases, challenging conventional patterns in bacterial resistance evolution. Our findings provide critical insights into the diverse pathways and mechanisms underpinning bacterial adaptation, underscoring the complexity of resistance evolution.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0071325"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753866","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":"Gut microbiota development, antibiotic resistome, and related perinatal factors in early infancy.","authors":"Pianpian Fan, Jinqian Ma, Qianwen Shen, Youcheng Ouyang, Ting Zhang, Jian Shen, Zhong-Cheng Luo, Zhiwei Liu, Fengxiu Ouyang","doi":"10.1128/msystems.00502-25","DOIUrl":"https://doi.org/10.1128/msystems.00502-25","url":null,"abstract":"<p><p>Early life is a critical window for gut microbiota development and antibiotic resistome. We aimed to investigate the microbiota longitudinal change during the first 6 months of life and the differences associated with assisted reproductive technology (ART) treatment, mode of delivery, and infant sex. Gut microbiota was measured by metagenomic sequencing of fecal samples repeatedly collected within 3 days after birth, at 42 days, 3 months, and 6 months in 155 Chinese infants. Among infants born by vaginal delivery, the ACE, Chao, and Sobs indexes increased with age. Accordingly, the relative abundance of <i>Actinobacteria</i> phylum increased from 43% ± 37% (mean ± SD) to 57% ± 36% and <i>Proteobacteria</i> phylum decreased from 48% ± 36% to 17% ± 25%; and <i>Bifidobacterium</i> and <i>Klebsiella</i> genus increased and <i>Escherichia</i> genus decreased, from the first 3 days to 6 months. The dominant antibiotic resistance genes were <i>macB</i> and <i>msbA</i>. Boys and girls had similar features. Infants born by cesarean section exhibited a similar gut microbiota developmental trajectory, but with a slower increase in alpha diversity over time, and lower <i>Bacteroidetes</i> phylum and <i>Bacteroides</i> genus at each age point. Compared with non-ART infants, ART infants had slightly higher alpha diversity indexes of ACE, Chao, Sobs, Shannon, and Pielou's evenness at age 42 days among infants born by vaginal delivery. Our findings confirm increasing diversity and composition evolution of gut microbiota in the first 6 months of life. Both modes of delivery and ART conception are associated with early gut microbiota alteration.IMPORTANCEGut microbiota plays an important role in various aspects of human health. Early life is a critical period for the development of gut microbiota. In this prospective study, we observed that the diversity and antibiotic resistance genes of gut microbiota increased gradually with age in the first 6 months of life. Boys and girls had similar features of gut microbiota. Cesarean section was associated with a lower abundance of <i>Bacteroidetes</i> phylum and <i>Bacteroides</i> genus. Compared with non-ART infants (spontaneous conception), ART infants had slightly higher alpha diversity indexes of ACE, Chao, Sobs, Shannon, and Pielou's evenness at age 42 days among infants born by vaginal delivery. This study presents gut microbiota development with age, antibiotic resistome, and related perinatal factors in early infancy.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0050225"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753862","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}