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PubMed2023

Exploiting Real-Time Genomic Surveillance Data To Assess 4CMenB Meningococcal Vaccine Performance in Scotland, 2015 to 2022.

The United Kingdom implemented the first national infant immunization schedule for the meningococcal vaccine 4CMenB (Bexsero) in September 2015, targeting serogroup B invasive meningococcal disease (IMD). Bexsero contains four variable subcapsular proteins, and postimplementation IMD surveillance was necessary, as nonhomologous protein variants can evade Bexsero-elicited protection. We investigated postimplementation IMD cases reported in Scotland from 1 September 2015 to 30 June 2022. Patient demographics and vaccination status were combined with genotypic data from the causative meningococci, which were used to assess vaccine coverage with the meningococcal deduced vaccine antigen reactivity (MenDeVAR) index. Eighty-two serogroup B IMD cases occurred in children >5 years of age, 48 (58.5%) of which were in unvaccinated children and 34 (41%) of which were in children who had received ≥1 Bexsero dose. Fifteen of the 34 vaccinated children had received one dose, 17 had received two doses, and two had received three doses. For 39 cases, meningococcal sequence data were available, enabling MenDeVAR index deductions of vaccine-preventable (M-VP) and non-vaccine-preventable (M-NVP) meningococci. Notably, none of the 19 of the children immunized ≥2 times had IMD caused by M-VP meningococci, with 2 cases of NVP meningococci, and no deduction possible for 17. Among the 15 children partially vaccinated according to schedule (1 dose), 7 were infected by M-VP meningococci and 2 with M-NVP meningococci, with 6 for which deductions were not possible. Of the unvaccinated children with IMD, 40/48 were ineligible for vaccination and 20/48 had IMD caused by M-VP meningococci, with deductions not being possible for 14 meningococci. IMPORTANCE This study demonstrates the value of postimplementation genomic surveillance of vaccine-preventable pathogens in providing information on real-world vaccine performance. The data are consistent with 2 and 3 doses of Bexsero, delivered according to schedule, providing good protection against invasive disease caused by meningococci deduced from genomic data to be vaccine preventable. Single doses provide poorer protection to infants. In practical terms, these data can provide public health reassurance when vaccinated individuals develop IMD with non-vaccine-preventable variants. They further indicate that additional testing is needed on variants for which no immunological data exist to improve estimates of protection, although these data suggest that the uncharacterized variants are unlikely to be covered by Bexsero. Finally, the confirmation that incomplete or absent doses in infancy lead to reduced protection supports public health and general practitioners in promoting vaccination according to schedule.

Infant↗
PubMed2015

Clonality and intracellular polyploidy in virus evolution and pathogenesis.

In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.

Animals↗
PubMed2006

Recent evolution of the human pathogen Cryptococcus neoformans by intervarietal transfer of a 14-gene fragment.

The availability of the whole-genome sequence from the 2 known varieties of the human pathogenic fungus Cryptococcus neoformans provides an opportunity to study the relative contribution of divergence and introgression during the process of speciation in a genetically tractable organism. At the genomic level, these varieties are nearly completely syntenic, share approximately 85-90% nucleotide identity, and are believed to have diverged approximately 18 MYA. Via a comparative genomic approach, we identified a 14-gene region (approximately 40 kb) that is nearly identical between the 2 varieties that resulted from a nonreciprocal transfer event from var. grubii to var. neoformans approximately 2 MYA. The majority of clinical and environmental var. neoformans strains from around the world contain this sequence obtained from var. grubii. This introgression event likely occurred via an incomplete intervarietal sexual cycle, creating a hybrid intermediate where mobile elements common to both lineages mediated the exchange. The subsequent duplication in laboratory strains of a fragment of this same genomic region supports evolutionary theories that instabilities in subtelomeric regions promote adaptive evolution through gene amplification and subsequent adaptation. Along with a more ancient predicted transfer event in C. neoformans and a recently reported example from Saccharomyces cerevisiae, these data indicate that DNA exchange between closely related sympatric varieties or species may be a recurrent theme in the evolution of fungal species. It further suggests that although evolutionary divergence is the primary force driving speciation, rare introgression events also play a potentially important role.

Chromosome Mapping↗
PubMed2026

Respiratory pandemic risk in the Anthropocene: A One Health framework and GISRS+ agenda.

Recent epidemics and pandemics caused by respiratory viruses, alongside the animal panzootic spread of highly pathogenic avian influenza A(H5Nx), have become a structural feature of the Anthropocene, yet responses remain largely reactive. This review integrates findings from WHO's Global Influenza Surveillance and Response System (GISRS) and related surveillance data (2000-2024), epidemiological studies of influenza A virus, SARS-CoV, MERS-CoV, SARS-CoV-2, and H5Nx, and One Health literature. We examine major groups of respiratory viruses and identify mismatches between risk and surveillance by focusing on spillover potential from animal hosts, human-to-human transmission and its controllability, and Anthropocene characteristics that increase epidemic risk. The analysis indicated that SARS-related coronaviruses and influenza A viruses, particularly H5Nx, are among the leading candidates based on currently available evidence because they have large reservoirs in animal hosts and spillover to humans is highly probable. The previous presymptomatic spread of SARS-CoV-2 and recent mammalian adaptation in H5N1 clade 2.3.4.4b highlight limitations of the traditional symptom-based and pathogen-specific surveillance system. Spillover events tend to occur in tropical and subtropical regions in low- and middle-income countries, but most genomic surveillance is in high-income countries. We propose interventions that address the upstream, midstream, downstream processes of epidemics. Upstream interventions are primary prevention measures related to land use, livestock, wildlife, and urban environments; midstream interventions are GISRS+-based pathogen-agnostic genomic and metagenomic early warning systems triggered by One Health; and downstream interventions include vaccines, antivirals, non-pharmaceutical interventions, and engineering with equity-centred global governance and sustainable financing.

Anthropocene↗
PubMed2006

Dendritic cell interactions and cytokine production.

The dendritic cell lineage comprises cells at various stages of functional maturation that are able to induce and regulate the immune response against antigens and thus function as initiators of protective immunity. The signals that determine the given dendritic cell functions depend mostly on the local microenvironment and on the interaction between dendritic cells and microorganisms. These interactions are complex and very different from one pathogen to another; nevertheless, both shared and unique responses have been observed using global genomic analyses. In this review, we have focused on the study of host-pathogen interactions using a genome-wide transcriptional approach with a focus on cytokine family members.

Animals↗
PubMed2002

Novel strategies in antifungal lead discovery.

There have been significant developments in fungal genomics over the past year. The recently released genome sequences of Aspergillus fumigatus and Cryptococcus neoformans have provided unprecedented opportunities for comparative genomics studies of many clinically relevant fungal pathogens. Emerging experimental analysis tools, such as fitness profiling and protein microarrays, have greatly enhanced our ability to conduct genome-wide functional studies.

Antifungal Agents↗
PubMed2006

Meningococcal genome dynamics.

Neisseria meningitidis (the meningococcus) is an important commensal, pathogen and model organism that faces up to the environment in its exclusive human host with a small but hyperdynamic genome. Compared with Escherichia coli, several DNA-repair genes are absent in N. meningitidis, whereas the gene products of others interact differently. Instead of responding to external stimuli, the meningococcus spontaneously produces a plethora of genetic variants. The frequent genomic alterations and polymorphisms have profound consequences for the interaction of this microorganism with its host, impacting structural and antigenic changes in crucial surface components that are relevant for adherence and invasion as well as antibiotic resistance and vaccine development.

Antigenic Variation↗
PubMed2026

Mannheimia haemolytica strain-level diversity in cattle populations.

High-resolution genomic characterization is essential for understanding diversity, pathogenicity, and transmission dynamics of bacterial pathogens. Mannheimia haemolytica (Mh) is the most consequential bacterial agent associated with bovine respiratory disease (BRD) in cattle, as a leading cause of morbidity, mortality, and antimicrobial use. Historically, BRD pathogens, including Mh, have been studied using culture or PCR approaches that provided limited ability to characterize fine-scale genomic variation across communities. Here, we evaluated target-enriched (TE) shotgun sequencing, a culture-independent method capable of strain-level resolution within metagenomic data, for detecting and characterizing Mh in comparison with qPCR and 16S rRNA gene sequencing. Nasal swabs (10 individual and 2 composited DNA samples per pen) and environmental samples (three ropes hung on pen rails and three water bowl swabs per pen) were collected from four pens in each of five distinct cattle populations. DNA was extracted for TE sequencing to identify Mh at both species and genomic sequence variant (GSV) levels, and to characterize antimicrobial resistance genes across the bacterial communities. qPCR was performed to quantify Mh genome copies, and 16S rRNA gene sequencing was used to assess the broader respiratory microbiome. TE sequencing identified Mh in 100% of TE-tested samples and classified multiple GSVs in all but 3 of 121 samples. GSV profiles clustered within housing groups and varied across cattle populations, indicating structured strain-level diversity. In contrast, Mannheimia spp. were detected in only 47.7% of samples by 16S rRNA sequencing. These findings demonstrate that TE sequencing enables sensitive, strain-level characterization of Mh in cattle and environmental samples and reveals substantial within-population genomic diversity not captured by conventional approaches.IMPORTANCETarget-enriched shotgun sequencing enabled sensitive, strain-level detection of Mannheimia haemolytica (Mh), revealing multiple co-circulating genomic sequence variants (GSVs) within and among cattle groups. This demonstrates greater genetic variability of Mh populations in beef cattle than has been previously recognized. The clustering of GSVs within housing groups, together with the overlap between respiratory and environmental samples, is consistent with the hypothesis that contagious transmission contributes to Mh ecology. These results highlight the potential utility of composite nasal swab and environmental samples for future studies evaluating relationships between Mh genomic variation and disease risk.

Animals↗
PubMed1999

High conservation of the fine-scale organisation of chromosome 5 between two pathogenic Leishmania species.

In a previous work we showed a remarkable conservation of the general structure of the genome (chromo-some number and synteny) among different pathogenic species of Old World Leishmania, indicating the absence of major interchromosomal rearrangements during evolution. In the present study, we have compared the fine structure of chromo-some 5 among two of these divergent species (Leishmania major and Leishmania infantum) by means of physical mapping. Remarkably, the 42 markers jointly mapped on these two chromosomes were found in an identical order along the chromosome. This perfect colinearity of the markers is in striking contrast to the large genetic distance that separates these species and suggests that conservation of the fine-scale organisation of chromosomes may be critical in Leishmania. If this colinearity is confirmed on the whole of the chromosome set, the current systematic sequencing programme of the genome of L.major should greatly help in the development of comparative genetics between different species of Leishmania.

Animals↗
PubMed2000

Challenge of investigating biologically relevant functions of virulence factors in bacterial pathogens.

Recent innovations have increased enormously the opportunities for investigating the molecular basis of bacterial pathogenicity, including the availability of whole-genome sequences, techniques for identifying key virulence genes, and the use of microarrays and proteomics. These methods should provide powerful tools for analysing the patterns of gene expression and function required for investigating host-microbe interactions in vivo. But, the challenge is exacting. Pathogenicity is a complex phenotype and the reductionist approach does not adequately address the eclectic and variable outcomes of host-microbe interactions, including evolutionary dynamics and ecological factors. There are difficulties in distinguishing bacterial 'virulence' factors from the many determinants that are permissive for pathogenicity, for example those promoting general fitness. A further practical problem for some of the major bacterial pathogens is that there are no satisfactory animal models or experimental assays that adequately reflect the infection under investigation. In this review, we give a personal perspective on the challenge of characterizing how bacterial pathogens behave in vivo and discuss some of the methods that might be most relevant for understanding the molecular basis of the diseases for which they are responsible. Despite the powerful genomic, molecular, cellular and structural technologies available to us, we are still struggling to come to grips with the question of 'What is a pathogen?'

Animals↗
PubMed1985

Cloning determinants of pathogenesis from Pseudomonas syringae pathovar syringae.

Transposon mutagenesis and a cosmid genomic library of DNA from the bean pathogen Pseudomonas syringae pathovar syringae were used to identify and isolate sequences essential for pathogenesis. Strain PS9021, derived by Tn5 mutagenesis, was determined to be nonpathogenic on Phaseolus vulgaris cultivar Red Mexican and incapable of inducing a hypersensitive response in Nicotiana tabacum. This mutant also produced fluidal rather than firm colonies on selected agar media. A Tn5-containing EcoRI fragment from PS9021 was cloned and used to probe 1500 members of a genomic library constructed with DNA from the pathogenic parent strain and the wide host range cosmid pVK102. One member that hybridized to the probe contained a cosmid with a 30-kilobase-pair insert (pOSU3101) that complemented the mutant phenotypes when mobilized into PS9021. A restriction endonuclease cleavage site map of pOSU3101 was constructed and sequences essential for pathogenesis were determined by subcloning. Approximately 8.5 kilobase pairs of the insert were essential for restoration by complementation of pathogenesis and hypersensitive response and wild-type colony morphology in strain PS9021.

Journal Article↗
PubMed2006

Antibacterial drug discovery--then, now and the genomics future.

Drug discovery research in the area of infectious diseases, in particular that dealing with antibacterial/antibiotic susceptibility and resistance, is in a process of continuing evolution. Steeped in the history of the highly successful intervention with chemotherapeutic agents to treat human infections, the emergence of drug-resistant pathogens worldwide presents a serious unmet medical need, if not a pending catastrophe. Research in both academia and industry over the past 30 years using molecular biology, genetics and more recently--bacterial genomics--has assembled key enabling technologies to increase productivity and success rates in the discovery and development of novel antibacterial agents. However genomics is not limited only to antibacterial target selection but provides the opportunity to further understand key interactions in the use of antibacterial compounds as therapeutic agents (such as resistance emergence, susceptibility, efflux, interactions between compound and pathogen, etc.). Genomics also offers the potential for insights into: bacterial niche adaptation, host susceptibility, treatment regimens, antibiotic resistance, pharmacokinetics (e.g., host metabolism differences), safety and the microbial genesis of chronic diseases (e.g., gastric ulceration).

Anti-Bacterial Agents↗
PubMed2025

Genomic and transcriptomic insights into the virulence and adaptation of shock syndrome-causing Streptococcus anginosus.

Streptococcus anginosus is a common isolate of the oral cavity and an opportunistic pathogen for systemic infections. Although the pyogenic infections caused by S. anginosus are similar to those caused by Streptococcus pyogenes, S. anginosus lacks most of the well-characterized virulence factors of S. pyogenes. To investigate the pathogenicity of S. anginosus, we analysed the genome of a newly identified S. anginosus strain, KH1, which was associated with toxic shock-like syndrome in an immunocompetent adolescent. The genome of KH1 contains nine genomic islands, two Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated systems and many phage-related proteins, indicating that the genome is influenced by prophages and horizontal gene transfer. Comparative genome analysis of 355 S. anginosus strains revealed a significant difference between the sizes of the pan genome and core genome, reflecting notable strain variations. We further analysed the transcriptomes of KH1 under conditions mimicking either the oral cavity or the bloodstream. We found that in an artificial saliva medium, the expression of a putative quorum quenching system and pyruvate oxidase for H2O2 production was upregulated, which could optimize the competitiveness of S. anginosus in the oral ecosystem. Conversely, in a modified serum medium, purine and glucan biosynthesis, competence and bacteriocin production were significantly upregulated, likely facilitating the survival of KH1 in the bloodstream. These findings indicate that S. anginosus can utilize diverse mechanisms to adapt to different environmental niches and establish infection, despite its lack of toxin production.

Streptococcus anginosus↗
PubMed1996

Haemophilus influenzae Genome: After Sequencing, Then What?

Haemophilus influenzae is an important human pathogen that causes a number of chronic and acute infections--notably, life-threatening bacteremia and meningitis in infants and community-acquired pneumonia in adults. The technological feat of sequencing the entire H influenzae genome was completed less than a year ago. Now that the genetic instruction manual is available, the task of deciphering its meaning has begun. This search will be a lengthy one, but it holds the promise of finding new ways to prevent, detect, and treat disease. The information gained will also shed light on mechanisms used by other bacterial pathogens and help to increase our understanding of how they cause disease.

Journal Article↗
PubMed2005

Deciphering the model pathogenic fungus Cryptococcus neoformans.

Cryptococcus neoformans is a basidiomycete fungal pathogen of humans that has diverged considerably from other model fungi such as Neurospora crassa, Aspergillus nidulans, Saccharomyces cerevisiae and the common human fungal pathogen Candida albicans. The recent completion of the genome sequences of two related C. neoformans strains and the ongoing genome sequencing of three other divergent Cryptococcus strains with different virulence phenotypes and environmental distributions should improve our understanding of this important pathogen. We discuss the biology of C. neoformans in light of this genomic data, with a special emphasis on the role that evolution and sexual reproduction have in the complex relationships of the fungus with the environment and the host.

Animals↗
PubMed2005

Replication-defective genomic HSV gene therapy vectors: design, production and CNS applications.

Herpes simplex virus (HSV) is a neurotropic double-stranded DNA virus. In an unmodified form it is a human pathogen, causing recurrent cold sores, keratitis and, rarely, severe encephalitis. Elimination of pathogenic functions results in the generation of a valuable gene transfer vector for neurological applications. Replication-defective genomic HSV-based vectors are highly infectious, and efficiently transduce and express transgenes in a broad range of both dividing and non-dividing cells. Clinically relevant yields of clinical grade vector can be produced by growth in cell lines that complement the viral functions that are deleted in the vectors to eliminate pathogenicity. The viral genome is over 150 kb in length and many of the viral genes may be deleted without compromising viral growth in vitro, and therefore large or multiple transgenes can be accommodated within the vectors. The wild-type virus adopts a lifelong latent state in neurons of sensory ganglia. This property can be exploited in the generation of vectors to allow long-term transgene expression in neurons. In this review, we summarize recent progress in the areas of vector development and vector production, and in developing gene transfer therapeutics to treat malignant glioma.

Animals↗
PubMed2002

A gene in the Pseudomonas syringae pv. tomato Hrp pathogenicity island conserved effector locus, hopPtoA1, contributes to efficient formation of bacterial colonies in planta and is duplicated elsewhere in the genome.

The ability of Pseudomonas syringae to grow in planta is thought to be dependent upon the Hrp (type III secretion) system and multiple effector proteins that this system injects into plant cells. ORF5 in the conserved effector locus of the P. syringae pv. tomato DC3000 Hrp pathogenicity island was shown to encode a Hrp-secreted protein and to have a similarly secreted homolog encoded in an effector-rich pathogenicity island located elsewhere in the genome. These putative effector genes were designated hopPtoA1 and hopPtoA2, respectively. DNA gel blot analysis revealed that sequences hybridizing with hopPtoA1 were widespread among P. syringae pathovars, and some strains, like DC3000, appear to have two copies of the gene. uidA transcriptional fusions revealed that expression of hopPtoA1 and hopPtoA2 can be activated by the HrpL alternative sigma factor. hopPtoA1 and hopPtoA1/hopPtoA2 double mutants were not obviously different from wild-type P. syringae pv. tomato DC3000 in their ability to produce symptoms or to increase their total population size in host tomato and Arabidopsis leaves. However, confocal laser-scanning microscopy of GFP (green fluorescent protein)-labeled bacteria in Arabidopsis leaves 2 days after inoculation revealed that the frequency of undeveloped individual colonies was higher in the hopPtoA1 mutant and even higher in the hopPtoA1/hopPtoA2 double mutant. These results suggest that hopPtoA1 and hopPtoA2 contribute redundantly to the formation of P. syringae pv. tomato DC3000 colonies in Arabidopsis leaves.

Amino Acid Sequence↗
PubMed2026

Convergence and global molecular epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus: a population genomic analysis.

BACKGROUND: Klebsiella pneumoniae is an important pathogen of humans and animals. In the past five years, increasing reports of convergent strains that carry both virulence factors and antimicrobial resistance genes (ARGs) have raised serious public health concerns. The aim of this study is to describe the global diversity of plasmids carrying iuc3 (a key virulence factor in K pneumoniae associated with pigs and clinical isolates) from diverse settings, and their role in the emergence of convergent strains through hybridisation with plasmids carrying ARGs. METHODS: This population genomic analysis study was designed to describe both the global and local diversity of iuc3-carrying plasmids from diverse sources, and the co-occurrence of iuc3 with ARGs. We used all 4148 Klebsiella spp isolates from two large One-Health studies (SpARK, Italy, and OH-DART, Thailand), including 191 Klebsiella isolates from pigs, 635 from clinical isolates, 1040 from hospital and community carriage, and 2282 from other sources. Short-read sequencing of Klebsiella isolates was performed as part of the SpARK study. We sequenced Klebsiella isolates from the OH-DART (MicrobesNG, Birmingham, UK; HiSeq and NovaSeq, Illumina San Diego, CA, USA; GridION, Oxford Nanopore Technologies, Oxford, UK) and SpARK (MinION or GridION, Oxford Nanopore Technologies, Oxford, UK) studies. We also retrieved plasmid sequences carrying iuc3 from the National Centre for Biotechnology Information (NCBI). To ascertain the degree of diversity, evolutionary dynamics, and structuring across ecological and geographical axes, we detected ARGs and virulence loci, analysed clustering patterns and generated approximate maximum-likelihood phylogenetic trees. FINDINGS: We identified 48 K pneumoniae isolates with iuc3 in the SpARK data and 79 in the OH-DART data. Three (2·4%) of these 127 isolates were from clinical sources, 73 (57·5%) were from pig or pork meat. iuc3 isolates corresponded to multiple (n=47) host sequence types (STs), with ST35, ST45, ST881, ST25, and ST967 harbouring iuc3 in both datasets. We generated hybrid assemblies for 44 (SpARK) and 36 (OH-DART) isolates, plus a single iuc3 isolate from Germany. 53 (65·4%) of these isolates were from pigs, three (3·7%) from clinical sources, and 25 (30·9%) from other sources. There were an additional 48 iuc3 positive isolates from our collections for which only short read data was available. A single iuc3-positive Klebsiella oxytoca isolate from a pig farm was detected in the SpARK data, which was also sequenced. We identified 330 iuc3-positive isolates and 58 iuc3-carrying plasmid assemblies from NCBI, of which 83 (21·4%) were from clinical sources, 120 from pigs (30·9%), and 185 (47·7%) from other sources or of unknown provenance. These isolates were from K pneumoniae except two isolates of Klebsiella quasipneumoniae subsp similipneumoniae and one of Enterobacter hormaechei. The combined dataset of 517 iuc3 plasmids ranged in size from 110 375 bp to 365 580 bp and mostly corresponded to multiple IncFIB(K) and IncFII replicon types. We found seven convergent K pneumoniae plasmids in the Thai data: six from fresh markets and one from a neighbouring hospital. These plasmids emerged through the hybridisation of cocirculating iuc3 plasmids and plasmids encoding extended-spectrum β-lactamases (ESBLs), although none of these seven plasmids carried genes encoding carbapenemases. We also identified putative cocirculating parental plasmids carrying iuc3 and ESBL-encoding genes. Clustering and phylogenetic analysis resolved the iuc3 plasmid sequences into three groups, which were consistent using both complete plasmid sequences (n=139) and short-read data (n=517). In the complete plasmid sequence data, 66 strains contained group 1 plasmids, 38 strains contained group 2 plasmids, and 35 strains contained group 3 plasmids. Group 3 plasmids are mostly carried by isolates circulating in hospitals throughout Asia, with occasional examples in Europe and elsewhere, and carry multiple ARGs and potential virulence factors. By contrast, group 1 plasmids are commonly carried by porcine isolates in Europe, and group 2 are a heterogeneous mixture of geographical and ecological sources. INTERPRETATION: Plasmid hybridisation occurs frequently outside of the health-care environment and can lead to the convergence of resistance and virulence traits. Generating complete plasmid sequences from regional population-scale samples facilitates the identification of convergent plasmids and their putative parental plasmids. Three robust groups of iuc3 plasmids were resolved, which show both epidemiological and geographical differences; one of these groups was associated with clinical isolates in Asia and warrants targeted plasmid surveillance. FUNDING: UKRI, JPIAMR, Evolution Education Trust, and a Schlumberger Foundation Fellowship.

Plasmids↗