Microbial Genomics最新文献

{"title":"Bile, sulphur and carbohydrate metabolic variation co-occur with host adiposity in mice colonized with primate microbiota.","authors":"Anthony T Pulvino, Maria Luisa Savo Sardaro, William G Quinn, Emma R Christopher, Sophie Koenig, Jordan M Lucore, Olivia Vidal-Cruchez, Elizabeth K Mallott, Sahana Kuthyar, Won Lee, Sriram Chitta, Stanton Gray, Lawrence E Williams, James P Curley, Emma R Liechty, Issam Ben-Sahra, Katherine R Amato","doi":"10.1099/mgen.0.001848","DOIUrl":"https://doi.org/10.1099/mgen.0.001848","url":null,"abstract":"<p><p>Although mechanistic links between the microbiome and chronic disease are increasingly well defined, how microbiomes facilitate normal variation in host metabolism remains less clear. Building on our recent demonstration that pooled faecal inocula from different primate species can cause relative differences in mouse host adiposity, we define potential mechanisms by which this could occur. Using existing samples from germ-free mice inoculated with faecal samples from humans (<i>Homo sapiens</i>), rhesus macaques (<i>Macaca mulatta</i>) and squirrel monkeys (<i>Saimiri boliviensis</i>), we integrate shotgun metagenomics of caecal contents, liquid chromatography-MS-MS metabolomics of serum and caecal contents and hepatic RNA-sequencing. Our multi-omic analysis reveals that the relative increase in adiposity previously observed in macaque-donor mice is associated with differences in hepatic cysteine catabolism and bile metabolism pathway features. These data suggest that bile and sulphur co-metabolic variation may mediate increased bile pool hydrophobicity. We also observed variation in caecal microbiome composition as well as host hepatic retinol signalling and lipid metabolism between treatments. When considered together with the observation that macaque-donor mice consumed less food than the other treatment groups, our results support the hypothesis that increased bile pool hydrophobicity results in increased dietary energy extraction. Our findings provide a foundation for future mechanistic testing of new hypotheses for understanding how the intestinal microbiomes of different primate species regulate lipid homeostasis in a mouse host.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182881","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 global epidemiology and evolution of <i>Escherichia coli</i> ST131 clade A.","authors":"Yasufumi Matsumura, Gisele Peirano, Pierre Bogaerts, Te-Din Huang, Bogdan I Iorga, Miki Nagao, Johann D D Pitout","doi":"10.1099/mgen.0.001858","DOIUrl":"10.1099/mgen.0.001858","url":null,"abstract":"<p><p>During the 2010s, <i>Escherichia coli</i> ST131 clade A tested sensitive to most antibiotics. In the 2020s, Europe experienced outbreaks of fluoroquinolone-resistant ST131-A that contained CTX-M β-lactamases and OXA-48-like carbapenemases. We investigated the acquisition of different antimicrobial resistance determinants in the emergence of multidrug-resistant (MDR) ST131-A. Phylogenetic analysis and Bayesian inference were utilized to define subclades and clusters (within subclades) and investigate the evolutionary history of ST131-A, using sequenced genomes and publicly available genomic data (<i>n</i>=2,905). ST131-A consisted of five dominant subclades and ten frequent clusters, representing 93 and 83% of the total population, respectively. The sampled most recent common ancestors of the dominant subclades dated mainly to the 1990s. Several MDR clusters linked with diverse quinolone resistance-determining region mutations, CTX-M and OXA-48-like genes diversified during the 2000s. The distribution and mobile genetic elements linked with <i>bla</i> _CTX-M-14, <i>bla</i> _CTX-M-15 and <i>bla</i> _CTX-M-27 differed among ST131-A subclades and clusters across geographic locations. Three ST131-A clusters belonging to different subclades and carrying <i>bla</i> _OXA-48 and <i>bla</i> _OXA-244 in distinct genetic contexts were associated with the recent European dissemination. The identification of MDR ST131-A subclades and clusters with divergent molecular architectures emerging independently across regions highlights the challenges for public health surveillance and control efforts.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Escherichia coli</i> ST131 isolates are rare in human meningitis but belong to a distinct O25b-<i>fim</i>H22 clade B lineage shared with avian pathogenic <i>Escherichia coli</i>.","authors":"Yasmine Benhadid-Brahmi, Guillaume Geslain, Kevin La, Stéphane Bonacorsi, Céline Courroux, Erick Denamur, Philippe Bidet, André Birgy","doi":"10.1099/mgen.0.001857","DOIUrl":"https://doi.org/10.1099/mgen.0.001857","url":null,"abstract":"<p><p><i>Escherichia coli</i> ST131 is a globally disseminated extraintestinal lineage best known for its resistance-driven expansion, yet it is rarely reported as a cause of neonatal meningitis. Whether specific ST131 sublineages retain neuroinvasive potential remains poorly understood. We analysed a 25-year nationwide French collection of 355 neonatal meningitis <i>E. coli</i> isolates recovered between 2000 and 2024. ST131 isolates were characterized by whole-genome sequencing, and ST131-O25b-<i>fim</i>H22 genomes were contextualized in a phylogeny including human-associated genomes and selected animal- and food-associated references. An extended dataset of 623 animal- and food-associated ST131-O25b-<i>fim</i>H22 genomes was analysed separately to assess the distribution of virulence-associated lineages across non-human reservoirs. Nine neonatal meningitis isolates belonged to ST131. Six were O25b:H4-<i>fim</i>H22 clade B isolates carrying K1, <i>invasion of brain endothelium</i> A (<i>ibe</i>A) and pS88-like markers; non-<i>fim</i>H22 isolates had heterogeneous virulence/resistance profiles, including two with <i>sen</i>B<i>-cjr</i>ABC-positive pRS218-like signatures. Phylogenomic analysis placed French ST131-O25b-<i>fim</i>H22 meningitis isolates within a conserved 85-genome lineage spanning 1995-2024 and comprising meningitis, bloodstream, urinary and avian-source isolates. This lineage was enriched in K1, <i>ibe</i>A, pS88-like signatures and virotype D/D4, with most isolates sharing HC100 assignment (≤100 core-genome allelic differences). The extended animal- and food-associated dataset identified a large poultry-associated HC100 population with the same K1/<i>ibe</i>A/pS88-like profile, whereas pRS218-like signatures were uncommon and mainly canine or feline. Although ST131 rarely causes neonatal meningitis, the isolates identified belong to a conserved ancestral ST131-O25b-<i>fim</i>H22 clade B lineage combining the major determinants of neonatal meningitis <i>E. coli</i> pathogenicity and are closely related to poultry-associated populations. Together with previous observations in ST95, these findings support a shared avian reservoir for highly pathogenic extraintestinal pathogenic <i>E. coli</i> lineages, distinct from the resistance-driven expansion of ST131-H30 and highlight the importance of One Health genomic surveillance.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128117","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":"Uncovering multidrug-resistance genes and potential biomarkers in <i>Klebsiella pneumoniae</i> using pan-genomic machine-learning feature-selection approach.","authors":"Thi Phuong Nguyen, Hsuan-Chia Yang, Yu-Wei Wu","doi":"10.1099/mgen.0.001851","DOIUrl":"https://doi.org/10.1099/mgen.0.001851","url":null,"abstract":"<p><p><b>Background.</b> Antimicrobial resistance is one of the biggest threats to modern medicine, yet our understanding of its genetic basis remains incomplete. Current surveillance strategies rely on established resistance genes catalogued in curated databases; however, bacterial populations continuously evolve resistance mechanisms that may not be recognized or characterized in those existing catalogues. Here, we combined pan-genomic analysis with machine-learning feature selection to identify genes significantly associated with antibiotic resistance in <i>Klebsiella pneumoniae</i> and to explore potential resistance determinants that have not been recognized before.<b>Results.</b> A total of 8,132 <i>K</i>. <i>pneumoniae</i> genomes were collected to construct a comprehensive pan-genome comprising >180,000 gene families. Using AdaBoost with an incremental feature-selection approach, we identified parsimonious gene sets (14-27 genes per antibiotic) that achieved high predictive accuracy (mean area under the receiver operating characteristic curve: 0.96; F₁-score: 0.93). Notably, about 15.8% of these genes were previously annotated as antimicrobial resistance determinants, whereas hypothetical proteins (HPs) and mobile genetic elements accounted for 32.5 and 22.3%, respectively. Among known resistance genes, we found that the <i>ble</i> gene, which encodes the bleomycin resistance protein, was widely associated with resistance to 8 of 12 included antibiotics. The functional re-annotation process also identified 15 HPs with diverse functions that are highly relevant to resistance, including transposases, components of the plasmid mobilization machinery, DNA manipulation proteins and regulatory factors. These findings underscore the importance of selecting and analysing highly associated features (or genes) in bacterial resistance.<b>Conclusion.</b> The study shows that pan-genomic analysis, coupled with feature selection, can uncover resistance-associated genes that conventional approaches miss. The findings also support enhancing surveillance strategies that incorporate emerging resistance mechanisms through large-scale genomic analysis, rather than relying exclusively on catalogued repertoires.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128116","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":"Plasmidomics: studying plasmids as ecological entities beyond their hosts.","authors":"Bradd Mendoza-Guido, Keilor Rojas-Jimenez","doi":"10.1099/mgen.0.001846","DOIUrl":"10.1099/mgen.0.001846","url":null,"abstract":"<p><p>Plasmids are mobile genetic elements with autonomous replication, whose ecology extends beyond individual bacterial hosts. As molecular symbionts, they have the potential to traverse bacterial taxa and environments, disseminating adaptive genes and shaping microbial community structure through dynamics that are likely decoupled from host taxonomy. Plasmidomics - the omics discipline dedicated to the study of plasmids - has revealed that plasmid diversity and distribution respond to environmental gradients independently of their hosts, underscoring their roles as ecological entities. However, the field faces critical methodological constraints: short-read assemblies fragment plasmid sequences, culture-dependent approaches underrepresent environmental diversity and most metagenomic methods fail to capture plasmid-host associations. In addition, a universally accepted classification framework is still lacking. Advancing plasmidomics will require the integration of long-read sequencing, Hi-C proximity ligation, meta-epigenomics and ecology-informed classification frameworks grounded in genomic and functional criteria. Together, these approaches are essential to uncover the true diversity, evolutionary significance and ecological dynamics of plasmids across complex microbial ecosystems.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome ecology and antibiotic treatment failure: resistance spread, microbial competition and community engineering.","authors":"Myles Wheeler, Erik Bakkeren","doi":"10.1099/mgen.0.001856","DOIUrl":"10.1099/mgen.0.001856","url":null,"abstract":"<p><p>The failure of antibiotic treatment is a growing concern, driven in large part by the rising incidence of antimicrobial resistance (AMR). Increasing evidence points to the importance of microbial competition in preventing the colonization of disease-causing pathogens and the spread of AMR. Crucially, the pathogens we target with antibiotics do not exist in isolation but instead compete and interact with the microbial communities that colonize the human body, microbiomes. Here, we therefore argue that the key to approaching the challenge of antibiotic treatment failure is understanding the strategies and mechanisms that microbes use to succeed in microbiomes. We discuss how microbial competition influences the colonization of pathogens and the spread of resistance via horizontal gene transfer. We then discuss how microbial competition may be used to synergize with antibiotic treatment or even replace it. Overall, we argue that studying microbial interactions offers a powerful approach to understanding and even mitigating antibiotic treatment failure.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep-sea Microbial Dataset of the Antarctic Ocean (dsMDAO): A high-resolution deep-sea microbial dataset of the Antarctic Ocean reveals potential for taxonomic and functional diversity.","authors":"Xingang Song, Shulei Jia, Lingling Chen, Chengjuan Cao, Zhongzhen Chen, Lingxiao Hang, Huihuang Jiang, Zhongwei Chen","doi":"10.1099/mgen.0.001847","DOIUrl":"https://doi.org/10.1099/mgen.0.001847","url":null,"abstract":"<p><p>Antarctic deep-sea ecosystems harboured unique and metabolically versatile micro-organisms that sustained key biogeochemical processes under extreme polar conditions. However, the genomic diversity and ecological functions of these sedimentary or deep-sea microbial communities remained largely unexplored. Here, we constructed a comprehensive deep-sea microbial dataset of the Antarctic Ocean (dsMDAO) by integrating three newly sequenced Prydz Bay sediment metagenomes with 22 publicly available datasets (9 seawater and 13 sediment samples), spanning water depths of ~300-3500 m. Genome binning yielded 186 metagenome-assembled genomes spanning 19 phyla, including 175 bacteria and 11 archaea, a substantial proportion of which represent previously uncharacterized species. Meanwhile, reads mapping with the available standard Kraken2 database (k2_standard) enabled the expansion of species richness of the dsMDAO database. Furthermore, functional annotation revealed diverse metabolic and ecological potentials, including carbon, nitrogen and sulphur cycling, as well as secondary metabolite biosynthesis, virulence-associated defence and cold-adaptation mechanisms. Sediment microbiomes exhibited higher phylogenetic and functional diversity, enriched in <i>Thaumarchaeota</i> and <i>Chloroflexi</i>, whereas seawater communities were dominated by <i>Proteobacteria</i> with more competitive biosynthetic and interaction potentials. Co-occurrence analyses further indicated complex and competitive networks in seawater versus modular and cooperative assemblages in sediments, reflecting distinct ecological strategies. Collectively, dsMDAO provides the first genome-resolved dataset of Antarctic deep-sea microbiota, revealing the hidden taxonomic and functional diversity that underpins ecosystem resilience in polar oceans. This resource lays a foundation for future ecological, evolutionary and biotechnological exploration of Antarctic microbial dark matter.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted genome recovery of under-sequenced microbes from the Sequence Read Archive STAT.","authors":"Harold P Hodgins, Briallen Lobb, Mackenzie Peck, Andrew C Doxey","doi":"10.1099/mgen.0.001853","DOIUrl":"https://doi.org/10.1099/mgen.0.001853","url":null,"abstract":"<p><p>Most microbial species are represented by a single genome in public databases. The lack of genomes for these 'singleton' organisms limits our understanding of their pan-genome diversity and evolution. Although the Sequence Read Archive (SRA) contains millions of sequencing datasets that could be used to expand our understanding of many species, the extent to which under-represented microbial species are present at levels sufficient for genome recovery is unclear. Here, we show that the pre-computed taxonomic profiles generated by the National Center for Biotechnology Information SRA Taxonomy Analysis Tool (STAT) can be used to identify SRA datasets containing recoverable genomes for under-represented microbes. Across >28 million SRA datasets, tens of thousands of singleton archaeal and bacterial species were detected, often at abundances consistent with successful genome recovery. Applying targeted genome recovery to 804 singleton species, we recovered genomes representing new strains for 472 species. The success rate of genome recovery correlated with STAT-derived estimates of genome coverage, demonstrating that genome recovery from the SRA is both predictable and scalable. Using the single available genome of <i>Clostridium tarantellae</i> as a case study, SRA data mining recovered seven additional <i>C. tarantellae</i> genomes, correcting assembly gaps in the reference genome, expanding its pan-genome and increasing its known host range by seven additional fish species. These findings reveal that many microbial species currently represented by a single genome are in fact widely distributed across existing sequencing data and highlight a major opportunity to systematically expand strain-level genomic diversity and pan-genomic representation for under-sampled microbial species without additional sequencing.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128044","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":"Members of the <i>Lactococcus-Pseudolactococcus</i> clade exhibit extensive genomic diversity in features associated with phage-host co-adaptation.","authors":"Axel Soto-Serrano, Jose Augusto Gonzales Castillo, Douwe van Sinderen, Lukasz Krych, Paulina Deptula, Jennifer Mahony","doi":"10.1099/mgen.0.001863","DOIUrl":"10.1099/mgen.0.001863","url":null,"abstract":"<p><p><i>Lactococcus lactis</i> and <i>Lactococcus cremoris</i> are widely exploited in global dairy fermentations. Consequently, strains of these species are extensively studied, as are their interactions with their infecting bacteriophages. In recent years, the number of lactococcal species has increased significantly and the ecology of these species extends far beyond the dairy niche. Furthermore, this expansion has also warranted the reassignment of several former lactococcal species to the genus <i>Pseudolactococcus</i>. In the present study, we explored the bacteriophage-relevant features of 495 genomes within the <i>Lactococcus-Pseudolactococcus</i> clade, including regions associated with (1) cell wall polysaccharides (CWPS) and exopolysaccharides (EPS) as possible bacteriophage receptors, (2) prophages and phage satellites and (3) anti-phage systems. This analysis revealed the universal presence and consistent genomic location of <i>cwps</i> loci, with extensive relationships between the loci of distinct species of both genera. It was also established that EPS-associated gene clusters are present in approximately half of the evaluated species and occur in a strain-dependent manner, suggesting that they are associated with niche adaptation rather than a core biological function of these organisms. Significant diversity and phylogenetic overlap of prophages across several species of both genera were observed. While prophages were widespread, phage satellites were especially prevalent among dairy-associated species. At the strain level, prophage, satellite and defence-system abundances were positively correlated. Restriction-modification systems appeared to form the core defence strategy of the <i>Lactococcus-Pseudolactococcus</i> taxon, complemented by species- and strain-level tailoring of the anti-phage repertoire to respond to phage pressure in diverse ecological niches. Niche-associated differences observed within <i>L. lactis</i> underscored that greater apparent phage exposure was not uniformly reflected across all phage-relevant features: dairy-associated strains carried more prophages, satellites and defence systems than plant-associated strains, whereas plant isolates exhibited greater rarefied polysaccharide pellicle richness. Overall, this represents the most comprehensive genome-based analysis of members of the <i>Lactococcus-Pseudolactococcus</i> clade, guiding our current understanding of the evolutionary pathways underlying phage-host co-adaptation followed by these micro-organisms.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic signatures associated with antibiotic resistance and predictive modelling in <i>Pseudomonas aeruginosa</i>.","authors":"Jianghong Cao, Gangli Zhang, Dongdong Xue, Dan Gao, Xiaoyang Li, Jinlin Guo, Peng Dai","doi":"10.1099/mgen.0.001854","DOIUrl":"https://doi.org/10.1099/mgen.0.001854","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is a major opportunistic pathogen with a remarkable capacity to develop resistance to multiple antibiotics. Although numerous resistance determinants have been characterized, broader genomic features associated with antibiotic resistance remain incompletely understood. In this study, more than 3 million CDSs were extracted from 7,801 <i>P</i>. <i>aeruginosa</i> genomes and clustered into a non-redundant CDS set comprising 87,744 centroid CDSs. Functional characterization of the CDSs was conducted using the Comprehensive Antibiotic Resistance Database, the Virulence Factor Database and KEGG annotations, and genome-wide enrichment analyses were performed to identify CDSs and functions associated with antibiotic resistance. Resistant strains generally carried more resistance- and virulence-associated CDSs than susceptible strains. Several CDSs encoding efflux pumps and antibiotic-modifying enzymes, e.g. <i>aad</i> genes, <i>tet(G</i>) and <i>cmlA9</i>, were significantly enriched in resistant strains. Pathway enrichment analyses revealed antibiotic-specific functional signatures, including porphyrin metabolism, sulphur metabolism and folate-related pathways among aminoglycoside-resistant strains, and homologous recombination, DNA replication and mismatch repair pathways among levofloxacin-resistant strains. However, polysaccharide production was enriched among CDSs nominally significantly associated with susceptible strains. Random forest models demonstrated moderate to excellent predictive performance with external validation confirming robustness. Co-occurrence network analyses further identified associations among virulence genes, e.g. between lipopolysaccharide biosynthesis- and O-antigen-associated genes, as well as associations between resistance determinants and virulence-associated genes, such as <i>β</i>-lactam resistance and iron acquisition genes. These findings revealed antibiotic-specific gene and pathway signatures, enabled the prediction of antibiotic resistance using genomic features and revealed potential genomic linkages between canonical resistance determinants and other resistance-associated features.</p>","PeriodicalId":18487,"journal":{"name":"Microbial Genomics","volume":"12 10","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111828","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}