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At least 19 recordsLinked to original sources

PubMed2025

Genomic structure of class 1 and 2 integrons in non-typhoidal Salmonella isolated from food animals and related meat products in the USA.

OBJECTIVES: Integrons facilitate the capture and expression of exogenous genes, including antimicrobial resistance (AMR) genes. This study aimed to detect the presence of integrons, examine their genomic structure and location, and analyse integron-associated AMR, virulence and stress response genes in Salmonella using WGS. METHODS: WGS data from 193 Salmonella strains, representing 38 serotypes isolated from food animals and related meat products (2001-2019), were analysed using bioinformatic tools to assess integron presence and characterize their genomic architectures. RESULTS: Of 193 isolates, 116 (60.1%) harboured class 1 and/or class 2 integrons. Class 1 integrons alone were detected in 105 isolates, with some containing multiple copies. One S. Infantis isolate harboured only class 2 integrons, whereas 10 others contained both classes. No class 3-5 integrons were found. Twenty-seven class 1 integrons were chromosomal; the rest were plasmid-associated, linked to various plasmid incompatibility (Inc) types. Sixty-nine distinct AMR genes conferring resistance to 11 antimicrobial classes were found in integron cassettes or integron-associated plasmids. Genes linked to resistance to quaternary ammonium compounds and heavy metals, as well as ISs and transposons, were also identified. Significant virulence and stress response genes and proteins such as groES-groEL, LysR and EAL (glutamate, alanine and leucine) were common in integron cassettes. CONCLUSIONS: Class 1 integrons are prevalent in MDR Salmonella isolates from food animals and related meat products and are linked to diverse plasmid types. Their association with AMR, virulence and stress response genes underscores their role in AMR dissemination, and bacterial adaptation and pathogenicity.

Integrons↗

PubMed2025

Distribution and molecular characterization of integron classes from Escherichia coli and Klebsiella pneumoniae isolates in Sulaymaniyah province of Iraq.

UNLABELLED: The environmental pollution from the misuse of antimicrobial drugs is fueling selection pressure in bacteria, thereby exacerbating the threat to global health. In Iraq, the situation is made worse by the poor implementation of the World Health Organization's Global Antimicrobial Resistance and Use Surveillance System (WHO-GLASS). Consequently, this study aimed to increase surveillance of the spread of antimicrobial resistance in Sulaymaniyah, Iraq. A total of 296 Enterobacteriaceae comprising 147 Klebsiella pneumoniae and 149 Escherichia coli were isolated from humans, poultry, and dairy farms. The isolates were screened using multiplex PCR to assess the prevalence of the clinically important integron integrase (intI) classes and antimicrobial resistance genes (ARGs) of commonly used antibiotics. Remarkably, 81.14% of the isolates carried at least 2 ARGs, 10.47% intI1, and 3.72% intI2. No intI3 was detected. A total of 663 ARGs were identified using multiplex PCR in the two Enterobacteriaceae: beta-lactamase genes were 43%, tetracycline resistance genes 25.20%, sulfonamide resistance gene 16.10%, quinolone resistance gene 10.2%, and aminoglycoside resistance genes 5.7%. K. pneumoniae harbored more integrons and ARGs than E. coli, thus posing a higher antimicrobial resistance threat in this province. This study underscores the importance of implementing more stringent WHO-GLASS and antibiotic stewardship to end the multidrug resistance crisis in Iraq. IMPORTANCE: These data are about the prevalence of integrons and resistance genes, helping to fill a significant gap in global surveillance efforts. Results can be used by global health authorities and the World Health Organization to develop national and international antimicrobial resistance (AMR) control strategies. The study is important because integrons are key genetic platforms that capture and disseminate antibiotic resistance genes among bacteria. In addition, Escherichia coli and Klebsiella spp. are among the top causes of hospital- and community-acquired infections, especially urinary tract infections, bloodstream infections, and pneumonia. Therefore, it will be riskier when these bacteria have a high rate of integrons and resistance genes because it impedes treatments during infection. Another importance of this study is that the study was carried out in Iraq. Iraq, like many low- and middle-income countries, faces challenges with unregulated antibiotic use, leading to high rates of AMR.

Escherichia coli↗

PubMed2026

High-throughput recovery of integron cassettes for gene discovery screens.

Integrons capture functional genes in mobile genetic elements called integron cassettes, which represent an untapped source of genes of biotechnological interest. Here we present two tools, cassette gatherer and cassette hunter, that enable high-throughput establishment of gene libraries either from genetically tractable strains or directly from DNA. We re-engineered a class 1 integron into counterselection markers on a plasmid or on the chromosome of a naturally competent Vibrio cholerae, which enabled capture of single cassettes in a sequence- and function-independent manner. When applied to Vibrio strains and genomic libraries, our tools recovered hundreds of single cassettes per assay with more than 99% specificity. We further subjected the library of cassettes generated by the hunter and gatherer tools to screens against phages ICP2 and T4, and identified nine phage-defence systems, including five previously undescribed. These tools enable rapid and large-scale recovery of integron cassettes that could be leveraged for functional gene discovery.

Journal Article↗

PubMed2026

Variations in carbapenem resistance associated with the VIM-1 metallo-β-lactamase across the Enterobacterales.

The VIM-1 metallo-β-lactamase enzyme, encoded within class 1 integrons, is found in Gram-negative clinical isolates worldwide and has been linked to outbreaks of bacterial pathogens in nosocomial settings. Six vim-1+ clinical isolates, from the genera Escherichia, Klebsiella and Enterobacter, were obtained from Kingston, Ontario, Canada. Whole-genome sequencing revealed that vim-1 was plasmid-borne in all strains and situated as the first gene in In916 or In110 integrons. Analysis of related plasmids suggested that these vim-1-containing plasmids are globally disseminated and have spread via horizontal gene transfer and autochthonous vertical spread within Ontario. Interestingly, the MICs of ertapenem and meropenem, two clinically relevant carbapenem antibiotics, against these six isolates varied more than tenfold, suggesting that the effects of VIM-1 are dependent on the genomic content of the host microbe. Introducing vim-1 into three common Enterobacterales laboratory strains was not sufficient to confer resistance to ertapenem and meropenem. Instead, adaptive laboratory evolution of the vim-1 + laboratory strains revealed that vim-1-mediated carbapenem resistance in these strains was dependent on epistatic interactions with ompC mutations, likely due to decreased outer membrane permeability to these antibiotics. Together, these results provide additional support for the role of gene epistasis in modulating the antimicrobial resistance phenotypes of acquired resistance genes, as well as previous results suggesting that the presence of a β-lactamase gene is insufficient to confer strong resistance to carbapenems without being paired with reduced outer membrane permeability.

beta-Lactamases↗

PubMed2026

Whole genome sequencing reveals the co-existence of blaPER-7, blaADC-52 and blaOXA-91 in multidrug resistant ST164pas/ST234oxfAcinetobacter baumannii strains in Bangladesh.

OBJECTIVE: Acinetobacter baumannii (A. baumannii) has emerged as a critical multidrug-resistant (MDR) pathogen with the capacity to persist in diverse ecological niches. Environmental reservoirs in densely populated settings such as Dhaka, Bangladesh, may play a significant role in sustaining and disseminating antimicrobial resistance (AMR). This study aimed to characterize the genomic and phenotypic features of MDR A. baumannii isolates recovered from urban water bodies. METHODS: Three environmental isolates of A. baumannii were subjected to antimicrobial susceptibility testing, biofilm and serum resistance assays, whole-genome sequencing and analysis. Comprehensive genome analysis was carried out emphasizing on antimicrobial resistance genes, virulence factor genes, multi-locus sequence type, integron, prophage and mobile genetic elements. RESULTS: Phenotypically, all the three isolates showed serum resistance and biofilm forming capacity. All the three isolates were identified as ST164pas/ST234oxf. The antimicrobial resistance genes investigation revealed that all the three isolates had co-existence of beta lactam resistance genes blaPER-7, blaADC-52 and blaOXA-91. The isolates had gyrA (S81L) and parC (V104I/D105E) mutations associated with fluoroquinolone resistance. Several prophage regions were found in the strains and A. baumannii ML1 harbored AMR genes inside prophage regions. All the isolates harbored integron 1 in their genome. Comparative genome analysis of the Bangladeshi ST164pas/ST234oxf strains revealed a high degree of genomic conservation. CONCLUSION: The findings from this study highlighted environmental water bodies as reservoirs for MDR A. baumannii and emphasize the need for targeted One Health surveillance and improved wastewater management to limit resistance dissemination.

Journal Article↗

PubMed2026

Deciphering the genomic landscape of novel Acinetobacter non-baumannii lineages causing neonatal septicemia: carbapenem resistance and virulence.

BACKGROUND: Acinetobacter non-baumannii (Anb) species are reported worldwide to cause infections in both adults and neonates, although less frequently than Acinetobacter baumannii. However, limited information is available on their genomic diversity, resistance mechanisms, and virulence potential. This study investigates novel Anb isolates causing neonatal septicemia in India to characterize their resistance and pathogenic traits. METHODS: Anb isolates from neonatal blood cultures (2007-2025) were identified by VITEK2 Compact system, MALDI-TOF MS, and Whole-genome sequencing (WGS). Antimicrobial susceptibility was tested by VITEK2. Genomic analysis included MLST, resistome, virulome, plasmid typing, integrons, and core-genome phylogeny analysis. In vitro and in vivo studies assessed pathogenic potential of Anb species. RESULTS: Anb infections were low (11%) among the neonates during the study period. WGS revealed 11 novel Sequence Types (STs) which include A. indicus, A. variabilis, A. schindleri, and A. bereziniae. Six out of these eleven Anbs harbored carbapenemases such as bla NDM-1 and/or bla OXA-58-like genes (bla OXA-58, bla OXA-420). bla NDM-1 was acquired via Tn125 transposon. ISAba125 was located upstream of bla NDM-1, and a conserved structure extending to IS91 family transposase was detected in bla NDM-1-harboring genomes. bla OXA-58-like genes were found to be associated with ISAba3. Most carbapenemases were likely located on chromosome. Class 1 integrons carrying multiple antimicrobial resistance genes (ARGs) and diverse plasmid replicase families were detected in Anbs. Core genome phylogeny showed that the study Anbs were not closely related to the global Anbs. In vitro virulence-associated assays (biofilm formation, surface motility, adherence/invasion, apoptosis) and in vivo lethality in murine infection model showed reduced pathogenicity, reinforcing earlier observations that Anb species are generally less virulent than A. baumannii. Several virulence factors (VFs) were detected; however, no clear correlation was observed between virulence genes, in vitro pathogenicity, and in vivo lethality. CONCLUSION: These results indicate the multifactorial nature of Anb pathogenicity and the current limitations of knowledge of its VFs. However, the presence of numerous VFs suggests a capacity to cause disease, particularly in vulnerable host populations such as neonates. Furthermore, the presence of multiple ARGs indicates a strong potential for persistence and dissemination in hospital environments with high antibiotic pressure. Overall, these findings underscore the importance of continued AMR surveillance, genome characterization and further investigations into Anb pathogenicity.

Acinetobacter non-baumannii↗

PubMed2026

Antibiotic Resistance Genes in Dust from Kindergarten Environments: A Systematic Review of Occurrence, Diversity, Determinants, and Exposure Implications.

Kindergarten environments combine high microbial exposure with increased immunological vulnerability, yet antibiotic resistance genes (ARGs) in kindergarten dust remain poorly characterized. This systematic review synthesized evidence on the occurrence and potential health relevance of ARGs in kindergarten dust. Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched. Four studies from China, Hong Kong, and Norway (2018-2024) met the inclusion criteria. ARGs were detected in all kindergarten dust samples, indicating that dust is a consistent reservoir of antibiotic resistance determinants. A consensus resistome (classes detected in ≥2 studies) encompassed sulfonamide, macrolide-lincosamide-streptogramin B (MLSB), tetracycline, beta-lactam, aminoglycoside, and multidrug resistance genes; beta-lactam resistance genes were the only class reported in all four studies. Clinically important ARGs associated with last-resort antibiotics, including mecA, vanA, blaNDM, and mcr-5, were reported in three studies. Class 1 integron-integrase genes (intI1) frequently co-occurred with ARGs, suggesting potential horizontal gene transfer. Limited evidence indicated higher ARG abundance in urban and winter samples. One study reported antibiotic-resistant bacteria carrying resistance markers concordant with those in kindergarten dust in the urine of children attending the same facilities; however, this cross-sectional, single-site evidence is consistent with, but not sufficient to establish, a dust-to-child exposure pathway. The available evidence supports the plausibility that kindergarten dust may contribute to children's exposure to ARGs and ARG-carrying bacteria, but current studies do not establish causal transmission from dust to child colonization or infection. Standardized monitoring and longitudinal studies are needed to assess health risks and guide mitigation strategies in early childhood educational settings.

Dust↗

PubMed2026

Genomic characterization of carbapenemase-producing Enterobacterales from wastewater reveals the convergence of KPC-2 and GES-16 in Brazil.

Carbapenemase-producing Enterobacterales (CPE) pose a significant public health concern due to the limited therapeutic options and increasing dissemination outside clinical settings. Wastewater treatment plants (WWTPs) have been proposed as relevant environmental reservoirs for antimicrobial-resistant bacteria and mobile genetic elements. In this study, we performed genomic characterization of CPE strains recovered from raw wastewater samples from the influents of different WWTPs. Antimicrobial susceptibility testing revealed multidrug resistance, including coresistance to carbapenems and polymyxins, among Klebsiella pneumoniae, Enterobacter asburiae, and Enterobacter kobei strains. Whole-genome sequencing identified the convergence of the blaKPC-2 and blaGES-16 genes, as well as the presence of blaGES-5 in E. kobei sequence type (ST) 540 strains. Moreover, the blaKPC-2 gene was detected in K. pneumoniae strains belonging to high-risk clones ST11 (capsular types KL64 and KL15) and ST307 (capsular type KL102), and E. asburiae ST384. The blaGES-5 and blaGES-16 genes were associated with class 1 integrons, while the blaKPC-2 gene was embedded within transposons (Tn4401a, Tn4401i, and Tn3-like) and insertion sequences (ISKpn27 and ISKpn6). Notably, genomic analyses and literature review demonstrated that the blaGES-16 gene remains unique to Brazil. The putative pathogenic potential of carbapenem-resistant K. pneumoniae ST11 was also assessed. These findings support the environmental circulation of clinically relevant Enterobacterales genotypes and emphasize the potential role of WWTPs as conduits for CPE dissemination, if not adequately operated. Therefore, genomic surveillance in extra-hospital settings may contribute to a better understanding of antimicrobial resistance ecology and inform One Health mitigation strategies.

Brazil↗

PubMed2025

Molecular characterization of antimicrobial resistance in Escherichia coli from dairy farm environment.

The present study was carried out to study the prevalence and genetic mechanisms of antimicrobial resistance in E. coli strains from dairy farms. A total of 60 E. coli strains were initially isolated from 192 dairy farm samples using a selective antibiotic approach and confirmed as E. coli by PCR. Among these, 48 E. coli isolates predominantly from fecal samples were further studied. These isolates were majorly classified in phylogroup A (43.75 %) and B1 (16.66 %) and showed predominant resistance against ampicillin (60.41 %) followed by piperacillin (56.25 %), tetracycline (54.16 %), and other β-lactams such as cefotaxime (47.91 %) and cefuroxime (43.75 %). A significant portion (22.9 %) of the E. coli isolates were multidrug-resistant (MDR) and 50 % were ESBL-positive. Multiple antibiotic resistance (MAR) index ≥0.4 was exhibited by three isolates. Genotypic analysis identified resistance genes associated with β-lactams (blaCTX-M-1, 64.58 %; blaTEM, 35.41 %; blaCTX-M-9, 4.16 %), tetracycline (tetA,37.58 %; tetB, 47.91 %), trimethoprim (dfrA17, 16.66 %), aminoglycosides [aac(6')-Ib-cr, 2.08 %] and fluoroquinolones [qnrB, 25 %; qnrS, 16.66 %; gyrB (S492N), 45.83 %; gyrA (S83L), 45.83 %; gyrA(S87L), 39.58 %; parC (S80I), 14.58 %]. E. coli isolates also showed a high frequency of mobile genetic elements (MGEs) such as IS26 (56.25 %), IncFIB plasmids (52.08 %), and Tn3 transposons (56.25 %). Class 1 integrons harbouring 200 and 800 bp gene cassettes were also detected in 5 E. coli isolates (10.4 %). Overall, this study highlights the high prevalence of diverse AMR genes in cattle-derived E. coli and their strong association with various MGEs. These findings emphasize the need for continuous genomic surveillance to mitigate resistance spread, particularly within and from dairy environments.

Escherichia coli↗

PubMed2026

Investigating AHL-associated quorum sensing impact on antibiotic-driven resistome expansion in anaerobic fermentation microbiomes: Metagenomic insights.

Previous studies have demonstrated that quorum sensing (QS) can mitigate the impact of antibiotics on environmental microbial communities. Metagenomic analysis was used to examine AHL effects on the resistome in anaerobic fermentation microbiomes under antibiotic stress in this research. AHLs reduced ARGs, MGEs, and phage abundance compared to antibiotic-only samples following the addition of high concentrations (500 nmol/L) of AHLs. Phages and integrons played pivotal roles in shaping the resistome. Escherichia coli, Vibrio cholerae, and Pseudomonas aeruginosa were key targets affected by AHLs. Both the assembled environmental metagenomes and the complete genomes of isolated bacteria consistently support the broad potential of quorum-sensing systems in mediating the dissemination or regulation of resistome spreading. Quorum sensing systems are very likely to affect microbial community resistomes by regulating the phageome. These insights are valuable for refining fermentation and waste management processes, offering potential in environmental restoration and possibly curbing the spread of resistance genes.

Quorum Sensing↗

PubMed2026

Genomic characterisation of ST233 Pseudomonas aeruginosa co-producing KPC-2 and VIM-2 in Northeastern Brazil during the COVID-19 pandemic: Evidence of independent horizontal acquisition events.

BACKGROUND: Dual-carbapenemase-producing Pseudomonas aeruginosa poses a major therapeutic and epidemiological challenge worldwide, yet systematic data on KPC and VIM co-production in Brazil remain limited. The COVID-19 pandemic intensified antimicrobial use, a period temporally associated with increased carbapenemase detection globally. OBJECTIVES: To characterise the molecular epidemiology and resistance profiles of KPC and VIM co-producing P. aeruginosa isolates from Brazil (2019-2023). METHODS: Between 2019 and 2023, 1489 multidrug-resistant P. aeruginosa isolates were screened by multiplex PCR for carbapenemase-encoding genes. Co-producing isolates underwent pulsed-field gel electrophoresis (PFGE) for clonal profiling, followed by whole-genome sequencing (WGS) for high-resolution phylogenomic analysis. Antimicrobial susceptibility testing and plasmid characterisation using next-generation sequencing platforms were also performed. RESULTS: Forty-two isolates (2.8%) harboured both blaKPC-2 and blaVIM-2, with detection occurring exclusively between 2020 and 2023, temporally coinciding with the COVID-19 pandemic. PFGE identified eight distinct clonal groups, providing evidence for independent horizontal gene transfer (HGT) events, whilst WGS confirmed all isolates as the high-risk ST233 lineage. Chromosomally integrated blaVIM-2 within class 1 integrons predominated; 2 isolates carried dual chromosomal copies. Plasmid-borne blaKPC-2 was identified across heterogeneous replicons (43.3-430.1 kb), suggesting multiple independent acquisition events. All co-producing isolates displayed extensive drug resistance, retaining in vitro susceptibility only to cefiderocol and colistin. CONCLUSIONS: ST233 co-producing KPC and VIM, represents a high-risk resistance phenotype of epidemiological significance. Divergent genomic architectures suggest active horizontal dissemination across diverse genetic backgrounds rather than clonal expansion, highlighting the need for enhanced surveillance and infection control strategies.

Bacterial genomic characterisation↗

PubMed2026

Emergence of a Tn7-associated blaVIM-1 within IncC plasmids in ST46 Providencia stuartii from Northern Italy.

OBJECTIVES: To characterize the genomic features and resistance determinants of carbapenem-resistant Providencia stuartii isolates circulating in Northern Italy, with a focus on the genetic context of blaVIM-1. METHODS: Five P. stuartii isolates collected between 2022 and 2024 from interconnected healthcare facilities underwent molecular characterization. Antimicrobial susceptibility testing was performed according to EUCAST 2025 criteria. Whole-genome sequencing was conducted using Illumina technology, followed by resistome, plasmidome, and phylogenetic analyses. Comparative genomics was used to investigate the genetic environment of blaVIM-1. RESULTS: All isolates belonged to the emerging ST46 lineage and exhibited an extensively drug-resistant phenotype, remaining susceptible only to amikacin. The blaVIM-1 gene was located on a ∼100 kb mobilizable IncC plasmid shared across all isolates. Notably, blaVIM-1 was embedded within a 13 kb Tn7 transposon carrying a complete set of transposition genes and inserted into a class 1 integron structure. Comparative analysis revealed no full homology with previously described IncC plasmids, suggesting a novel genetic arrangement. Phylogenetic analysis demonstrated close relatedness among Italian isolates (<33 SNPs), supporting local clonal circulation, while showing clear separation from previously described NDM-producing ST46 strains. CONCLUSIONS: This study describes the rare association of blaVIM-1 with a Tn7 transposon in P. stuartii, highlighting the genomic plasticity of IncC plasmids and their role in the emergence of new resistance platforms. The identification of this structure in a high-risk lineage underscores the potential for further dissemination of carbapenem resistance in healthcare settings.

IncC↗

PubMed2025

Global emergence and transmission dynamics of carbapenemase-producing Citrobacter freundii sequence type 22 high-risk international clone: a retrospective, genomic, epidemiological study.

BACKGROUND: Carbapenemase-producing Citrobacter (CPC) species have recently been recognised as emerging pathogens associated with nosocomial infections in humans. The increased rate of Citrobacter freundii infections is a public health concern and there is a paucity of genomic data regarding its global transmission dynamics. We aimed to characterise the genetic features of CPC species, and their associated carbapenemase-encoding plasmids, obtained from hospitalised patients in China and from publicly available global data, with a particular focus on high-risk clones. METHODS: This was a retrospective, genomic epidemiological study of CPC species obtained from a tertiary hospital in Zhejiang Province, China, from March 5, 2013, to March 5, 2023. We used antimicrobial susceptibility testing, short-read and long-read whole-genome sequencing, phylogenomic analysis, and plasmid structure analysis. A global dataset of complete plasmid sequences encoding blaKPC, blaNDM, and blaIMP was constructed from the National Center for Biotechnology Information (NCBI) RefSeq database to provide insights into their diversity and distribution. All carbapenemase-producing Citrobacter freundii genomes from the NCBI GenBank database were incorporated in the comparative genomic analyses. Bayesian phylogeographical analysis and growth rate assays were carried out to characterise the high-risk C freundii sequence type (ST) 22 clone. FINDINGS: 1724 Citrobacter species isolates were collected from diverse clinical specimens, with 48 identified as CPC species. Citrobacter koseri (22 [46%] of 48) and C freundii (20 [42%]) were the predominant CPC species. Comparative analysis found C freundii carried significantly higher median numbers of plasmid replicons (5·0 [IQR 3·3-6·0] vs 2·0 [2·0-3·0]; p<0·0001) and acquired antimicrobial resistance genes (12·0 [7·3-15·8] vs 3·0 [3·0-5·3]; p<0·0001) than did C koseri. Molecular characterisation identified Inc-type plasmids, In823::Kl.pn.I3/In1589-like/In837-like integrons, Tn6296/Tn125/Tn5060 transposons, and insertion sequences (eg, IS26, IS3000, IS5, ISAba125, ISCR1), collectively facilitating the dissemination of carbapenemase genes. Global analysis of 3126 carbapenemase-encoding plasmids found epidemic plasmids with broad host ranges and global diversity. Phylogenetic investigation of predominant carbapenemase-encoding plasmids showed their persistence across geographical regions, temporal spans, and Enterobacterales species, exhibiting high genetic similarity to our clinical plasmids. A phylogenetic tree of 726 global carbapenemase-producing C freundii genomes showed that ST22 (227 [31·3%]) represents the predominant multidrug-resistant clone across community, health-care, and environmental niches. Transmission across continents contributes to the global predominance of the ST22 clone, which carries a high load of resistance genes (median 15·0 [IQR 11·0-17·0] vs 12·0 [3·0-16·0]; p<0·0001) and enhanced plasmid maintenance capacity (median replicons 5·0 [IQR 4·0-7·0] vs 4·0 [3·0-6·0]; p<0·0001) relative to non-ST22 clones. INTERPRETATION: Our study provides evidence to suggest that Citrobacter species are emerging carriers of carbapenem-resistance genes. These findings provide insight into the population structure of CPC species and highlight C freundii ST22 as a prominent high-risk international clone. FUNDING: National Natural Science Foundation of China, National Health Commission Scientific Research Fund-Zhejiang Provincial Major Health Science and Technology Plan Project, Zhejiang Province Natural Science Foundation Project, Outstanding Youth Foundation of Jiangsu Province of China, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Postgraduate Research and Practice Innovation Program of Jiangsu Province.

Citrobacter freundii↗

PubMed2026

Treatment strategies for imipenemase-producing Gram-negative infections: lessons from Japan.

Carbapenems remain essential for treating serious infections caused by drug-resistant Gram-negative bacteria because of their broad-spectrum activities and favourable safety profiles. However, the emergence of carbapenemase-producing Enterobacterales, which produce enzymes that efficiently hydrolyse β-lactams including carbapenems, continues to undermine their clinical utility. Although new antibiotics such as ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, and cefiderocol have expanded therapeutic options, their effectiveness varies substantially across different carbapenemase families. Carbapenemases produced by Enterobacterales include serine β-lactamases (Ambler classes A and D) and metallo-β-lactamases (MBLs; Ambler class B), each with distinct substrate and inhibitor profiles. Clinically relevant MBLs-including imipenemase (IMP), New Delhi MBL (NDM), and Verona integron-encoded MBL (VIM) variants-show markedly different biochemical properties and inhibitor susceptibilities. Despite their clinical relevance, optimal treatment strategies for infections caused by IMP-producing Enterobacterales remain poorly defined. The unique reactivity of IMP-type MBLs to inhibitors differs from that of other MBLs such as NDMs or VIMs, underscoring the need for tailored therapeutic approaches. In this Personal View, we summarise current evidence and, drawing on Japan's experience as an endemic setting for IMP producers, outline key scientific, clinical, and public health challenges that should be addressed globally to develop effective, evidence-based treatment strategies for IMP-producing Enterobacterales infections.

Humans↗

PubMed2026

Novel bacterial hosts and mobile genetic structure of tet(X) variants in tetracycline-contaminated aquatic environment uncovered by culture and long-read metagenomics.

Clinically important tigecycline (3rd-generation tetracycline) resistance tet(X) variants were inferred to have evolutionarily originated from environmental bacteria, and have been recognized among environment, human and animals. However, genetic basis for environmental proliferation and dissemination of tet(X) variants remains ambiguous. This study profiled tet(X) variants at gene, contig, isolate, and community levels in environmental community subjected to long-term stepwise increasing oxytetracycline (1st-generation tetracycline) or tigecycline pressure using long-term microcosm experiments, quantitative PCR, bacterial isolation, whole-genome sequencing, and Nanopore-based long-read metagenomics. We confirmed that both oxytetracycline and tigecycline enriched the abundance of tetracycline resistance genes especially oxytetracycline-enriched tet(X3). Unexpectedly diverse bacterial hosts and genetic structure of tet(X)-positive mobile elements in the environment microbiome were identified using bacterial isolation and long-read Nanopore metagenomics. Pseudomonas defluvii was first reported to carry tet(X3) in the chromosome, forming IS26-tet(X3)-res-ISCR2 circular intermediate to transfer between different DNA molecules. Database mining revealed similar mobile segments have prevailed among animal-derived Acinetobacter species. Unlike the widely reported ISCR2-mediated transfer of tet(X6), we identified a novel mobile multidrug transposon TnAs3 where tet(X6) and class 1 integron co-transferred as its passenger region. Mobile tet(X2)-ere(D)-aadS-erm(F)-blaOXA-347 segment was annotated in Runella, and co-occurrences of tet(X2) and ere(D), aadS, blaOXA-347 were also found in Flavobacterium, Arsenicibacter, Chryseobacterium and Pedobacter. Overall, tetracycline-contaminated aquatic microbiome harboured diverse mobile tet(X)-positive segments which have not yet been acquired by clinical pathogens, and thus served as the genetic pool of tet(X) variants together with indigenous bacterial hosts, especially the newly reported Pseudomonas defluvii. Reducing pollution of older-generation tetracyclines would be a proactive way to mitigate environmental evolution and possible clinical effects of tet(X) variants.

Metagenomics↗

PubMed2025

Comparative in vitro activity of ceftazidime-avibactam plus aztreonam and the fixed combination aztreonam/avibactam against multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVES: MDR Pseudomonas aeruginosa is difficult to treat, despite some new beta-lactam/beta-lactamase inhibitors. A combination of ceftazidime-avibactam and aztreonam (CAZ/AVI + AZT) is frequently used to treat Gram-negative bacteria expressing metallo-beta-lactamases. A fixed combination of aztreonam/avibactam was recently licenced for use in Europe, but it remains unknown whether there are differences between both options for use against P. aeruginosa. This study evaluates the comparative in vitro efficacy of the fixed combination aztreonam/avibactam compared to the three antibiotics CAZ/AVI + AZT against clinical MDR P. aeruginosa isolates. METHODS: MICs for aztreonam/avibactam and CAZ/AVI + AZT were determined in 38 MDR P. aeruginosa isolates recovered from routine diagnostics using broth microdilution with checkerboard assays in triplicates as the reference method. Fractional inhibitory concentration (FIC) indices were calculated. Whole-genome sequencing was performed on all isolates. RESULTS: At a fixed ceftazidime concentration of 8 mg/L (EUCAST breakpoint), 25 isolates exhibited lower MICs for CAZ/AVI + AZT compared to aztreonam/avibactam alone in microdilution assays. On FIC analysis, additive and synergistic effects were seen in 28 and 2 cases, respectively. Verona integron-encoded metallo-beta-lactamase (VIM) was the most prevalent carbapenemase (21/38 isolates), followed by Imipenemase (IMP, 4/38) and New Delhi metallo-beta-lactamase (NDM, 2/38). Lower MICs were observed for the combination CAZ/AVI + AZT in isolates carrying VIM-2 as compared to VIM-1. CONCLUSIONS: In vitro testing of CAZ/AVI + AZT revealed increased in vitro susceptibility among MDR P. aeruginosa isolates in comparison to the fixed combination of aztreonam/avibactam.

Pseudomonas aeruginosa↗

PubMed2026

Emergence of Acinetobacter soli harboring three carbapenemase-encoding genes (blaNDM-1, blaIMP-14, and blaOXA-58) on a single plasmid in an ICU patient.

Acinetobacter soli is an environmentally adaptable species increasingly recognized as an emerging pathogen in hospital settings, particularly in intensive care units (ICUs). In this study, we report the first A. soli isolate from an ICU patient that co-harbors three carbapenemase-encoding genes (blaNDM-1, blaIMP-14, and blaOXA-58) on a single plasmid. Whole-genome sequencing revealed that multidrug resistance in this strain is mediated by a 294,790 bp plasmid, pSLAB-A, carrying 16 antimicrobial resistance genes, including all three carbapenemases. Comparative plasmid analysis showed a highly conserved backbone but identified a unique ~40 kb multidrug-resistance region containing blaNDM-1, blaIMP-14, and eight additional resistance genes. Genetic context analysis indicated that insertion sequences (ISAba125 and ISAba3) and class 1 integrons contribute to the mobilization and accumulation of carbapenemase-encoding genes. Plasmid stability assays demonstrated that pSLAB-A remained stably maintained for more than 90 generations without antibiotic selection. A global survey of the NCBI database identified 15 A. soli strains carrying carbapenemase-encoding genes, most of which were isolated from China, with clinical specimens representing the predominant source. Seven carbapenemase-encoding genes were detected, with blaNDM-1 being the most prevalent. Among eight isolates with complete genomes, all carried carbapenemase-encoding genes on plasmids. Phylogenetic analysis revealed regional dissemination of a clonal lineage across hospitals in Zhejiang Province and sustained nosocomial transmission within a hospital in Taiwan. These findings suggest that the spread of carbapenem resistance in A. soli is largely driven by multidrug-resistance plasmids, facilitating clonal expansion in hospital environments and posing a growing challenge for antimicrobial therapy and infection control in ICUs.IMPORTANCECarbapenem-resistant A. soli is an emerging clinical concern, capable of causing severe invasive infections, including bacteremia, in intensive care unit settings, and its emergence poses substantial challenges to antimicrobial therapy. In this study, we demonstrate that carbapenem resistance in A. soli is predominantly mediated by the acquisition of multidrug-resistance plasmids carrying carbapenemase-encoding genes. Owing to its strong environmental persistence, A. soli can readily undergo nosocomial clonal dissemination once carbapenem resistance is acquired. Moreover, the spread of multidrug plasmids co-harboring multiple carbapenemase-encoding genes may accelerate the evolutionary trajectory of resistance in A. soli, further exacerbating the threat to clinical management. Given its demonstrated capacity to cause hospital-associated infections and to rapidly acquire multidrug resistance, A. soli warrants heightened vigilance from both clinical and public health perspectives.

beta-Lactamases↗

PubMed2026

Mobile genetic elements-driven partitions of mega-plasmids resistome in Salmonella Infantis.

Salmonella enterica serovar Infantis (S. Infantis) becomes the primary pathogen among the top Salmonella serotypes, contributing to numerous cases of foodborne illness annually in the United States. S. Infantis infection has spread rapidly worldwide, especially the clones with pESI-like plasmids. However, the underlying mechanisms regarding the transmission of S. Infantis, particularly mobile genetic elements (MGEs), mediated horizontal gene transfer, are limited. The objective of this study was to evaluate the relationship, if any, among MGEs, antibiotic-resistant genes (ARGs), and virulence factors (VFs) within S. Infantis via genomic analysis. A total of 91 S. Infantis complete genomes with high sequencing quality were selected for downstream bioinformatic analysis. The results showed that the majority of VFs were located in the bacterial chromosomes, while most ARGs were carried by S. Infantis mega-plasmids in an MGE-favored manner. Integrons and transposons were closely associated with certain ARGs, but prophages within mega-plasmids displayed a diverse ARG profile. Collectively, MGE-mediated horizontal gene transfer might lead to ARG acquisition by mega-plasmids, subsequently contributing to the resistome of S. Infantis. Our findings provide insights into the development of MGE-associated resistome in S. Infantis that could inform more effective prevention and intervention strategies to control this pathogen, further ensuring public health and safety.IMPORTANCEThe rapid emergence and transmission of antibiotic-resistant foodborne pathogens pose a significant risk to public health, necessitating the discovery of underlying mechanisms to control multidrug-resistant pathogens. Salmonella enterica serovar Infantis (S. Infantis) has become a pathogen of clinical and epidemiological relevance in recent years, ranking as the top prevalent serovar associated with foodborne illnesses and exhibiting resistance to several antibiotics. The current investigation of multidrug resistance (MDR) S. Infantis strains primarily emphasized the presence of mega-plasmids. However, the question of how mega-plasmids contribute to the transmission of antibiotic-resistant genes (ARG) is unaddressed. Utilizing the genomic characterization of S. Infantis complete genomes with high quality, our study revealed that the resistome of S. Infantis mega-plasmids-the primary ARG reservoirs of S. Infantis-followed a specific pattern of mobile genetic elements (MGEs). Monitoring the spread of MGE-carried ARGs within mega-plasmids should be considered in future surveillance.

Interspersed Repetitive Sequences↗