mSystems最新文献

{"title":"A call for the United States to continue investing in science.","authors":"Ira Blader, Felicia Goodrum, Michael J Imperiale, Arturo Casadevall, Cesar Arias, Andreas Baumler, Carey-Ann Burnham, Christina Cuomo, Corrella Detweiler, Graeme Forrest, Jack Gilbert, Susan Lovett, Stanley Maloy, Alexander McAdam, Irene Newton, Gemma Reguera, George A O'Toole, Patrick D Schloss, Ashley Shade, Marvin Whiteley","doi":"10.1128/msystems.00275-25","DOIUrl":"https://doi.org/10.1128/msystems.00275-25","url":null,"abstract":"","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0027525"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515919","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":"Revealing pathogenesis-associated metabolites in <i>Histoplasma capsulatum</i> through comprehensive metabolic profiling.","authors":"Adrian Heckart, Jean-Christophe Cocuron, Stephanie C Ray, Chad A Rappleye, Ana P Alonso","doi":"10.1128/msystems.00186-25","DOIUrl":"https://doi.org/10.1128/msystems.00186-25","url":null,"abstract":"<p><p>During infection, <i>Histoplasma capsulatum</i> yeasts interact with a variety of phagocytic cells, where macrophages represent an important niche for long-term intracellular fungal survival and replication. In the phagosomes of macrophages, a hostile environment where most microorganisms are killed, <i>Histoplasma</i> not only survives but overcomes several biological challenges and proliferates intracellularly. To better understand the characteristics of intracellular <i>Histoplasma</i> and the phagosomal environment, a metabolomic platform was used to analyze <i>Histoplasma</i> yeasts cultured on different carbon sources and yeasts extracted from macrophages, identifying metabolites associated with pathogenesis. Metabolomic results of <i>in vitro</i>-grown yeasts were further characterized with available transcriptomic data, informing underlying gene expression patterns in response to contrasting milieus. These approaches revealed that <i>Histoplasma</i> yeasts, unlike many other yeasts, do not ferment sugars to ethanol, and, when cultivated on glycolytic versus gluconeogenic carbon sources, produce distinct metabolomes with altered intracellular amino acid, lipid, and sugar contents. Furthermore, analysis of <i>Histoplasma</i>-inoculated media illustrated that <i>Histoplasma</i> secretes mannitol and anthranilates. Lastly, a comparison of the metabolomes derived from <i>in vitro</i> cultivation versus intracellular growth highlighted leucine and cysteine/cystine as amino acids, which may serve as sources of carbon, nitrogen, and sulfur to yeasts within macrophages. These results detail metabolites linked to <i>Histoplasma</i> metabolism during macrophage infection, identifying potential candidates to target for novel histoplasmosis therapeutics.IMPORTANCEIntracellular pathogens reside within host cells, surviving against innate immune responses while exploiting host resources to proliferate. Understanding the mechanisms that underlie their survival and proliferation is critical for developing novel treatments and therapeutics for the diseases these pathogens cause. While <i>Histoplasma</i> is a unique example of a true intra-phagosomal pathogen, insights into its pathogenesis may still inform the study of other intracellular pathogens.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0018625"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516145","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":"Emerging <i>Clostridioides difficile</i> ribotypes have divergent metabolic phenotypes.","authors":"Firas S Midani, Heather A Danhof, Nathanael Mathew, Colleen K Ardis, Kevin W Garey, Jennifer K Spinler, Robert A Britton","doi":"10.1128/msystems.01075-24","DOIUrl":"10.1128/msystems.01075-24","url":null,"abstract":"<p><p><i>Clostridioides difficile</i> is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although <i>C. difficile</i> is a genetically diverse species, certain ribotypes are overrepresented in human infections, and it is unclear if metabolic adaptations are essential for the emergence of these epidemic ribotypes. To identify ribotype-specific metabolic differences, we therefore tested carbon substrate utilization by 88 <i>C</i>. <i>difficile</i> isolates and looked for differences in growth between 22 ribotypes. As expected, <i>C. difficile</i> was capable of growing on a variety of carbon substrates. Further, <i>C. difficile</i> strains clustered by phylogenetic relationship and displayed ribotype-specific and clade-specific metabolic capabilities. Surprisingly, we observed that two emerging lineages, ribotypes 023 and 255, have divergent metabolic phenotypes. In addition, although <i>C. difficile</i> Clade 5 is the most evolutionary distant clade and often detected in animals, it displayed robust growth on simple sugars similar to Clades 1-4. Altogether, our results corroborate the generalist metabolic strategy of <i>C. difficile</i> but also demonstrate lineage-specific metabolic capabilities.IMPORTANCEThe gut pathogen <i>Clostridioides difficile</i> utilizes a wide range of carbon sources. Microbial communities can be rationally designed to combat <i>C. difficile</i> by depleting its preferred nutrients in the gut. However, <i>C. difficile</i> is genetically diverse with hundreds of identified ribotypes, and most of its metabolic studies were performed with lab-adapted strains. To identify ribotype-specific metabolic differences, we profiled carbon metabolism by a myriad of <i>C. difficile</i> clinical isolates. While the metabolic capabilities of these isolates clustered by their genetic lineage, we observed surprising metabolic divergence between two emerging lineages. We also found that genetically newer and older clades grew to a similar level on simple sugars, which contrasts with recent findings that newer clades experienced positive selection on genes involved in simple sugar metabolism. Altogether, our results underscore the importance of considering the metabolic diversity of pathogens in the study of their evolution and the rational design of therapeutic interventions.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0107524"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516125","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":"Anaerobic digestion of microalgae: microbial response and recovery after organic loading disturbances.","authors":"Juline M Walter, Silvia Greses, Live H Hagen, Valerie C Schiml, Phillip B Pope, Cristina González-Fernández, Magnus Ø Arntzen","doi":"10.1128/msystems.01674-24","DOIUrl":"https://doi.org/10.1128/msystems.01674-24","url":null,"abstract":"<p><p>Industrial anaerobic digestion (AD) represents a relevant energy source beyond today's fossil fuels, wherein organic matter is recycled to methane gas via an intricate and complex microbial food web. Despite its potential, anaerobic reactors often undergo process instability over time, which is frequently caused by substrate composition perturbations, making the system unreliable for stable energy production. To ensure the reliability of AD technologies, it is crucial to identify microbial and system responses to better understand the effect of such perturbations and ultimately detect signatures indicative of process failure. Here, we investigate the effect of the microalgal organic loading rate (OLR) on the fermentation product profile, microbiome dynamics, and disruption/recovery of major microbial metabolisms. Reactors subjected to low- and high-OLR disturbances were operated and monitored for fermentation products and biogas production over time, while microbial responses were investigated via 16S rRNA gene amplicon data, shotgun metagenomics, and metagenome-centric metaproteomics. Both low- and high-ORL fed systems encountered a sudden decline in methane production during OLR disturbances, followed by a recovery of the methanogenic activity within the microbiome. In the high-OLR disturbances, system failure triggered an upregulation of hydrolytic enzymes, an accumulation of fermentation products, and a shift in the methanogenic population from hydrogenotrophic to acetoclastic methanogens, with the latter being essential for recovery of the system after collapse.</p><p><strong>Importance: </strong>Anaerobic digestion (AD) with microalgae holds great potential for sustainable energy production, but process instability caused by substrate disturbances remains a significant barrier. This study highlights the importance of understanding the microbial dynamics and system responses during organic loading rate perturbations. By identifying key shifts in microbial populations and enzyme activity, particularly the transition from hydrogenotrophic to acetoclastic methanogens during recovery, this research provides critical insights for improving AD system stability and can contribute to optimizing microalgae-based AD processes for more reliable and efficient methane production.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0167424"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515940","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":"Long-read transcriptomics of caviid gammaherpesvirus 1: compiling a comprehensive RNA atlas.","authors":"Gábor Torma, Ákos Dörmő, Ádám Fülöp, Dóra Tombácz, Máté Mizik, Amanda M Pretory, See-Chi Lee, Zsolt Toth, Zsolt Boldogkői","doi":"10.1128/msystems.01678-24","DOIUrl":"10.1128/msystems.01678-24","url":null,"abstract":"<p><p>Caviid gammaherpesvirus 1 (CaGHV-1), formerly known as the guinea pig herpes-like virus, is an oncogenic gammaherpesvirus with a sequenced genome but an as-yet uncharacterized transcriptome. Using nanopore long-read RNA sequencing, we annotated the CaGHV-1 genome and constructed a detailed transcriptomic atlas. Our findings reveal diverse viral mRNAs and non-coding RNAs, along with mapped promoter elements for each viral gene. We demonstrated that the CaGHV-1 RTA lytic cycle transcription factor activates its own promoter, similar to Kaposi's sarcoma-associated herpesvirus (KSHV), and that the CaGHV-1 ORF50 promoter responds to RTA proteins from other gammaherpesviruses, highlighting the evolutionary conservation of RTA-mediated transcriptional mechanisms. Additionally, our analysis uncovered extensive transcriptional overlap within the viral genome, suggesting a role in regulating global gene expression. Given its tumorigenic properties, broad host range, and non-human pathogenicity, this work establishes CaGHV-1 as a promising small animal model for investigating human gammaherpesvirus pathogenesis.</p><p><strong>Importance: </strong>The molecular underpinnings of gammaherpesvirus pathogenesis remain poorly understood, partly due to limited animal models. This study provides the first comprehensive transcriptomic atlas of CaGHV-1, highlighting both coding and non-coding RNAs and revealing regulatory elements that drive viral gene expression. Functional studies of the CaGHV-1 RTA transcription factor demonstrated its ability to self-activate and cross-activate promoters from homologous gammaherpesviruses, reflecting conserved mechanisms of transcriptional control. These findings solidify CaGHV-1 as a unique and versatile small animal model, offering new opportunities to investigate gammaherpesvirus replication, transcriptional regulation, and tumorigenesis in a controlled experimental system.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0167824"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516085","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":"Association of tumor microbiome with survival in resected early-stage PDAC.","authors":"Yixuan Meng, Chan Wang, Mykhaylo Usyk, Soyoung Kwak, Chengwei Peng, Kenneth S Hu, Paul E Oberstein, Michelle Krogsgaard, Huilin Li, Richard B Hayes, Jiyoung Ahn","doi":"10.1128/msystems.01229-24","DOIUrl":"https://doi.org/10.1128/msystems.01229-24","url":null,"abstract":"<p><p>The pancreas tumor microbiota may influence tumor microenvironment and influence survival in early-stage pancreatic ductal adenocarcinoma (PDAC); however, current studies are limited and small. We investigated the relationship of tumor microbiota to survival in 201 surgically resected patients with localized PDAC (Stages I-II), from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts. We characterized the tumor microbiome using RNA-sequencing data. We examined the association of the tumor microbiome with overall survival (OS), via meta-analysis with the Cox PH model. A microbial risk score (MRS) was calculated from the OS-associated microbiota. We further explored whether the OS-associated microbiota is related to host tumor immune infiltration. PDAC tumor microbiome α- and β-diversities were not associated with OS; however, 11 bacterial species, including species of <i>Gammaproteobacteria</i>, confirmed by extensive resampling, were significantly associated with OS (all <i>Q</i> < 0.05). The MRS summarizing these bacteria was related to a threefold change in OS (hazard ratio = 2.96 per standard deviation change in the MRS, 95% confidence interval = 2.26-3.86). This result was consistent across the two cohorts and in stratified analyses by adjuvant therapy (chemotherapy/radiation). Identified microbiota and the MRS also exhibited association with memory B cells and naïve CD4⁺ T cells, which may be related to the immune landscape through BCR and TCR signaling pathways. Our study shows that a unique tumor microbiome structure, potentially affecting the tumor immune microenvironment, is associated with poorer survival in resected early-stage PDAC. These findings suggest that microbial mechanisms may be involved in PDAC survival, potentially informing PDAC prognosis and guiding personalized treatment strategies.IMPORTANCEMuch of the available data on the PDAC tumor microbiome and survival are derived from relatively small and heterogeneous studies, including those involving patients with advanced stages of pancreatic cancer. There is a critical knowledge gap in terms of the tumor microbiome and survival in early-stage patients treated by surgical resection; we expect that advancements in survival may initially be best achieved in these patients who are treated with curative intent.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0122924"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515963","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":"Evolutionary trajectory of bacterial resistance to antibiotics and antimicrobial peptides in <i>Escherichia coli</i>.","authors":"Feiyu Yu, Dejuan Wang, Haijie Zhang, Zhiqiang Wang, Yuan Liu","doi":"10.1128/msystems.01700-24","DOIUrl":"https://doi.org/10.1128/msystems.01700-24","url":null,"abstract":"<p><p>The global crisis of antimicrobial resistance poses a major threat to human health, underscoring the urgency of developing new antibacterial strategies. Antimicrobial peptides (AMPs) are promising alternatives to antibiotic therapy, yet potential microbial resistance is of great concern. Resistance is often accompanied by fitness costs, which may in turn influence the spread of drug-resistant bacteria and their susceptibility to other antimicrobial agents. Herein, we investigate the evolutionary trajectory of bacterial resistance to antibiotics and AMPs in <i>Escherichia coli</i>, and evaluate the fitness costs and collateral sensitivity of drug-resistant strains. We reveal that <i>E. coli</i> develops resistance to antibiotics, particularly ciprofloxacin and kanamycin, at a notably faster rate than to AMPs. Moreover, antibiotic-evolved strains exhibit slightly higher fitness costs than AMP-evolved bacteria, primarily manifested in reduced bacterial growth and swimming motility. Notably, we demonstrate that trimethoprim-resistant <i>E. coli,</i> with mutations in <i>thyA</i> gene, displays enhanced susceptibility to pexiganan, as evidenced by both <i>in vitro</i> and <i>in vivo</i> studies. Overall, our findings shed new insights for the clinical deployment of AMPs and propose innovative therapeutic strategies for combating antibiotic-resistant bacterial infections.IMPORTANCEThe global spread of antimicrobial resistance necessitates the development of innovative anti-infective strategies. Antimicrobial peptides (AMPs) represent promising alternatives in the post-antibiotic era. By monitoring the evolutionary trajectory of bacterial resistance to eight antibiotics and ten AMPs in <i>Escherichia coli</i>, we demonstrate that <i>E. coli</i> exhibits slower emergence of resistance against AMPs compared with antibiotics. Additionally, these antibiotic-resistant strains incur significant fitness costs, particularly in bacterial growth and motility. Most importantly, we find that some antibiotic-resistant strains show collateral sensitivity to specific AMPs in both <i>in vitro</i> and animal infection models, which is conducive to accelerating the development of AMP-based antibacterial treatment.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0170024"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516078","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":"Multi-omics analysis reveals associations between gut microbiota and host transcriptome in colon cancer patients.","authors":"Yuling Qin, Qiang Wang, Qiumei Lin, Fengfei Liu, Xiaolan Pan, Caibiao Wei, Junxian Chen, Taijun Huang, Min Fang, Weilong Yang, Linghui Pan","doi":"10.1128/msystems.00805-24","DOIUrl":"https://doi.org/10.1128/msystems.00805-24","url":null,"abstract":"<p><p>Colon cancer (CC) is one of the most common cancers globally, which is associated with the gut microbiota intimately. In current research, exploring the complex interaction between microbiomes and CC is a hotspot. However, the information on microbiomes in most previous studies is based on fecal, which does not fully display the microbial environment of CC. Herein, we collected mucosal and tissue samples from both the tumor and normal regions of 19 CC patients and clarified the composition of mucosal microbiota by 16S rRNA and metagenomic sequencing. Additionally, RNA-Seq was also conducted to identify the different expression genes between tumor and normal tissue samples. We revealed significantly different microbial community structures and expression profiles to CC. Depending on correlation analysis, we demonstrated that 1,472 genes were significantly correlated with CC tumor microbiota. Our study reveals a significant enrichment of <i>Campylobacter jejuni</i> in the mucosa of CC, which correlates with bile secretion. Additionally, we observe a negative correlation between <i>C. jejuni</i> and immune cells CD4+ Tem and mast cells. Finally, we discovered that metabolic bacterial endosymbiont of <i>Bathymodiolus</i> sp., <i>Bacillus wiedmannii</i>, and <i>Mycobacterium tuberculosis</i> had a significant survival value for CC, which was ignored by previous research. Overall, our study expands the understanding of the complex interplay between microbiota and CC and provides new targets for the treatment of CC.</p><p><strong>Importance: </strong>This study contributes to our understanding of the interaction between microbiota and colon cancer (CC). By examining mucosal and tissue samples rather than solely relying on fecal samples, we have uncovered previously unknown aspects of CC-associated microbiota. Our findings reveal distinct microbial community structures and gene expression profiles correlated with CC progression. Notably, the enrichment of <i>Campylobacter jejuni</i> in CC mucosa, linked to bile secretion, underscores potential mechanisms in CC pathogenesis. Additionally, observed correlations between microbial taxa and immune cell populations offer new avenues for immunotherapy research in CC. Importantly, this study introduces CC-associated microbiota with survival implications for CC, expanding therapeutic targets beyond conventional strategies. By elucidating these correlations, our study not only contributes to uncovering the potential role of gut microbiota in colon cancer but also establishes a foundation for mechanistic studies of gut microbiota in colon cancer, emphasizing the broader impact of microbiota research on cancer biology.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0080524"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516141","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":"Analysis of co-occurrence of type II toxin-antitoxin systems and antibiotic resistance determinants in <i>Staphylococcus aureus</i>.","authors":"Michał Bukowski, Michał Banasik, Kinga Chlebicka, Katarzyna Bednarczyk, Emilia Bonar, Dominika Sokołowska, Tomasz Żądło, Grzegorz Dubin, Benedykt Władyka","doi":"10.1128/msystems.00957-24","DOIUrl":"https://doi.org/10.1128/msystems.00957-24","url":null,"abstract":"<p><p>Toxin-antitoxin (TA) systems consist of toxic proteins and their inhibitors, and were originally shown to ensure plasmid maintenance in bacterial populations. Over time, however, TA systems have also been identified on bacterial chromosomes, raising questions about their roles unrelated to plasmid stability. Among the eight currently recognized types of TA systems, type II has been the most extensively investigated. Type II systems are often found in pathogenic bacterial species, including staphylococci. <i>Staphylococcus aureus</i>, a notorious human pathogen, harbors multiple type II TA systems, both plasmid- and chromosome-encoded, while their potential relation to virulence remains to be addressed. Here, we investigate the co-occurrence of TA systems and antibiotic resistance (AR) determinants in <i>S. aureus</i>, focusing on the potential negative impact of type II toxin RNases on antibiotic resistance. We considered both well-characterized and newly characterized TA loci of <i>S. aureus</i>. Our findings demonstrate a relationship between TA systems and AR determinants, wherein TA systems negatively affect antibiotic resistance. Due to substantial selective pressure, the migration of TA systems from plasmids to chromosomes results in their inactivation. This observation may be an important factor shaping the spread and evolution of both TA systems and AR determinants in bacteria. We exemplify this phenomenon in detail using the well-known PemIK-Sa1 system and a newly identified SCCmec-related PemIK-Sa6 system characterized in this study.</p><p><strong>Importance: </strong>Toxin-antitoxin (TA) systems are entities unique to bacteria. They are involved in the maintenance of mobile genetic elements (MGEs), regulation of gene expression and bacterial virulence. <i>Staphylococcus aureus</i> is a dangerous human pathogen with increasing antibiotic resistance (AR). The maintenance and dissemination of AR determinants is often driven by MGEs, which link AR and TA systems. Our study identified a negative correlation between TA systems and AR determinants in <i>S. aureus</i>. Furthermore, we have shown that the expression of a toxic component of an exemplary TA system negatively affects antibiotic resistance. We argue that in particular strains, a selective pressure maintains either the TA system or AR determinant. Alternatively, TA systems are inactivated by mutations when present together with AR determinants to maintain the functionality of the latter. Our observations uncover an important factor shaping the spread and evolution of both TA systems and AR determinants in bacteria, which is especially relevant to pathogenic species.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0095724"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515942","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 flavonoid-sensing regulator AefR is involved in modulating quorum sensing through repressing the MexEF-OprN efflux pump in <i>Pseudomonas fluorescens</i>.","authors":"Yu Xiao-Quan, Han Jian-Ting, Feng Han-Zhong, Hou Jun, Wang Zhi-Ping, Yong-Xing He","doi":"10.1128/msystems.00915-24","DOIUrl":"https://doi.org/10.1128/msystems.00915-24","url":null,"abstract":"<p><p>Flavonoids, a major component of plant root exudates, play a crucial role in mediating plant-microbe interactions. However, the mechanisms by which flavonoids are perceived and trigger downstream signaling events in microbes remain largely unknown. In this study, we characterized AefR, a flavonoid-sensing transcriptional regulator from <i>Pseudomonas fluorescens</i> 2P24, a plant growth-promoting rhizobacterium (PGPR) known for its biocontrol properties. AefR was found to repress the expression of the mexEF-oprN efflux pump, which putatively exports N-acylhomoserine lactones (AHLs). This repression attenuates the PcoR/PcoI quorum-sensing system, leading to decreased production of the antibiotic mupirocin in <i>P. fluorescens</i> 2P24. Furthermore, quantitative proteomic analysis revealed that the PcoR/PcoI quorum-sensing system regulates a diverse range of physiological processes, including mupirocin production and denitrification. Collectively, these findings demonstrate a quorum-quenching role of flavonoids in a PGPR strain, establishing that flavonoids can disrupt quorum-sensing by enhancing the efflux of quorum-sensing signaling molecules. These findings have practical implications for the development of sustainable biocontrol strategies, where leveraging natural plant-microbe interactions could enhance the suppression of plant pathogens without the use of synthetic chemicals.IMPORTANCEFlavonoids are key mediators of plant-microbe interactions; however, their role in regulating microbial signaling remains poorly understood. This study identifies AefR as a flavonoid-sensing regulator in <i>Pseudomonas fluorescens</i> 2P24, revealing a novel quorum-quenching mechanism where flavonoids enhance the efflux of quorum-sensing signals. These findings shed light on the molecular basis of flavonoid-mediated microbial regulation and offer new strategies for sustainable plant health management.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0091524"},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516148","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}