Global emergence of Carbapenem-resistant Hypervirulent Klebsiella pneumoniae driven by an IncFIIK34 KPC-2 plasmid

EBioMedicine, Год журнала: 2025, Номер 113, С. 105627 - 105627

Опубликована: Март 1, 2025

SummaryBackgroundCarbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has been increasingly reported worldwide, posing a severe challenge to public health; however, the mechanisms driving its emergence and global dissemination remain unclear.MethodsWe analysed CR-hvKp strains derived from canonical hvKp backgrounds, acquired carbapenemase-encoding gene. These were identified 485 CRKp isolates in CRACKLE-2 China cohort, 259 multi-centre study, 67,631 K. genomes available GenBank. Clinical harbouring IncFIIK34 KPC-2 plasmid selected for genome sequencing, RNA-Seq, conjugation assays, vivo, ex vitro phenotypic characterisation.FindingsAnalysis of clinical 414 24 countries GenBank an as prevalent KPC (detected 25%, 45/178 KPC-producing CR-hvKp). Compared with epidemic IncFIIK2 plasmid, exhibited 100- 1000-fold increase frequency (10−4–10−5 vs. 10−7) growth advantage under meropenem challenge–likely due overexpression conjugation-related genes increased blaKPC copy number expression. transconjugants carrying this often reduced mucoviscosity, while retaining hypervirulence both murine models human neutrophil assays.InterpretationThe may be key factor CR-hvKp, underscoring urgent need enhanced molecular surveillance emerging pathogen.FundingNational Natural Science Foundation National Institutes Health.

Язык: Английский

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Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 6, 2024

Abstract Bacterial evolution is affected by mobile genetic elements like phages and conjugative plasmids, offering new adaptive traits while incurring fitness costs. Their infection the bacterial capsule. Yet, its importance has been difficult to quantify because of high diversity confounding mechanisms in genomes such as anti-viral systems surface receptor modifications. Swapping capsule loci between Klebsiella pneumoniae strains allowed us their impact on plasmid phage independently background. Capsule swaps systematically invert susceptibility, revealing serotypes key determinants infection. types also influence conjugation efficiency both donor recipient cells, a mechanism shaped volume pilus structure. Comparative genomics confirmed that more permissive lab correspond acquiring plasmids nature. The least capsule-sensitive pili (F-like) are most frequent species’ only ones associated with antibiotic resistance virulence factors, driving convergence antibiotics population. These results show how cellular envelopes define slow fast lanes elements, implications for population dynamics horizontal gene transfer.

Язык: Английский

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Plasmid-encoded insertion sequences promote rapid adaptation in clinical enterobacteria

Nature Ecology & Evolution, Год журнала: 2024, Номер 8(11), С. 2097 - 2112

Опубликована: Авг. 28, 2024

Язык: Английский

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Identification of novel origins of transfer across bacterial plasmids

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 30, 2024

ABSTRACT Conjugative plasmids are important drivers of bacterial evolution, but most lack genes for conjugation. It is currently not known if the latter can transfer because origins by conjugation ( oriT ), which would allow their mobilization conjugative plasmids, poorly known. Here, we identify and characterize occurrences families across thousands confirming that mobilizable still identifiable oriTs . They reveal clear patterns in terms intergenic position, distance to relaxases, MOB-type association. This allowed develop a computational method discover novel s. As proof concept, 21 from nosocomial pathogens Escherichia coli , Klebsiella pneumoniae Acinetobacter baumannii some them responsible mobility critical antimicrobial resistance genes. These share key characteristics others fill missing diversity relaxase-encoding both frequency phylogeny. We confirmed experimentally function six them. The ability s paves way explore notably among majority lacking conjugation-related

Язык: Английский

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Interspecific competition can drive plasmid loss from a focal species in a microbial community

The ISME Journal, Год журнала: 2023, Номер 17(10), С. 1765 - 1773

Опубликована: Авг. 10, 2023

Plasmids are key disseminators of antimicrobial resistance genes and virulence factors, it is therefore critical to predict reduce plasmid spread within microbial communities. The cost carriage a metric that can be used plasmids' ecological fate, unclear whether costs affected by growth partners in community. We carried out competition experiments tracked maintenance using model system consisting synthetic stable five-species community broad host-range plasmid, engineered carry different payloads. report both the its long-term focal strain depended on presence competitors, these interactions were species specific. Addition increased high-payload strain, accordingly, loss from occurred over shorter time frame. propose destabilising effect interspecific may leveraged clinical natural environments cure plasmids strains.

Язык: Английский

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Intra- and Interspecies Conjugal Transfer of Plasmids in Gram-Negative Bacteria

Biomedicines, Год журнала: 2025, Номер 13(1), С. 238 - 238

Опубликована: Янв. 20, 2025

Background/Objectives: Plasmid-mediated resistance is a significant mechanism that contributes to the gradual decrease in efficacy of antibiotics from various classes, including carbapenems. The aim this study investigate frequency transfer carbapenemase-encoding plasmids K. pneumoniae E. coli and P. aeruginosa. Methods: Matings were performed on agar with subsequent isolation transconjugant, recipient, donor colonies. conjugation (CF) minimum inhibitory concentrations (MICs) meropenem determined for PCR-confirmed transconjugants. A pharmacodynamic was conducted using hollow-fiber infection model transconjugant order evaluate its viability presence therapeutic meropenem. Results: CF pneumoniae-K. similar pneumoniae-E. higher MIC donor. MICs transconjugants (0.25–4 μg/mL) compared recipients (0.03–0.06 μg/mL). aeruginosa did not acquire pneumoniae. In experiments, an 2 mg/L within “susceptibility range”, failed respond treatment. Conclusions: between falls range. permissiveness pneumoniae, i.e., same species, observed. Conjugation occur borderline susceptibility may pose potential threat

Язык: Английский

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Cutting-edge tools for unveiling the dynamics of plasmid–host interactions

Trends in Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Deletion of pcnB affects antibiotic susceptibility in resistant Escherichia coli by reducing copy number of ColE1-family plasmids

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 11, 2025

Plasmids play a major role in the spread of antibiotic resistance genes bacteria. Plasmid copy number (PCN) is often tightly regulated. In plasmids ColE1-type, this regulation happens by negative feedback mechanism using an antisense RNA. Here, we employed sequencing-based method for determining PCN to demonstrate that different ColE1-family harboring increases during treatment. Further, show deletion gene pcnB reduces E. coli MG1655, which turn results reduced antimicrobials classes aminoglycosides, β-lactams and tetracyclines. absence selection, also decreased ColE1-type bacterial population. Hence, PcnB, polyadenylates RNA, marking it decay, represents potential drug helper-drug target could be used reduce re-sensitize bacteria with multi-copy-number resistance-plasmids treatment antimicrobials.

Язык: Английский

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Plasmid conjugation drives within–patient plasmid diversity

Microbial Genomics, Год журнала: 2025, Номер 11(3)

Опубликована: Март 20, 2025

Plasmids are well-known vehicles of antimicrobial resistance (AMR) gene dissemination. Through conjugation, plasmid-encoded AMR genes spread among neighbouring bacteria, irrespective their strain or even species. This process is very concerning from a public health perspective, as plasmid-borne outbreaks often not confined to single species strains and therefore more difficult fully uncover. At the moment, impact plasmid conjugation on within–patient diversity well understood. In this work, we will tackle role using dataset carbapenemase-producing Enterobacterales . The 256 sequences originates bacterial isolates cultured 115 English patients over 30 months. Each patient has than one sequence, with at least sequence carrying an OXA-48 gene, carbapenemase-encoding gene. If carries they carried in different hosts. Using hybrid de novo –on-reference assembly pipeline, were able reconstruct full short read sequencing data for 232 sequences. Of patients, 83 (72%) had identical two Only ( > 200 SNPs) alleles plasmid, probably separate acquisitions. Our study shows that when host found patient, it most likely same been shared via conjugation. event acquisition plasmids hosts highly unlikely our dataset.

Язык: Английский

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Plasmid-driven strategies for clone success in Escherichia coli

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 3, 2025

Язык: Английский

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