Emergence of IS26-mediated pLVPK-like virulence and NDM-1 conjugative fusion plasmid in hypervirulent carbapenem-resistant Klebsiella pneumoniae

Tian, Chongmei; Shi, Yueyue; Ren, Lingzhi; Huang, Di; Wang, Siwei; Zhao, Yaping; Fu, Liping; Bai, Yang; Xia, Daozong; Fan, Xueyu

doi:10.1016/j.meegid.2023.105471

Cited by 2 publications

(1 citation statement)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A significant finding from our research lies in the identification of specific conjugative helper plasmids, not only contributing to the MDR phenotype but also offering a means for the horizontal transfer of the non-conjugative virulence plasmid between K. pneumoniae isolates. These helper plasmids shared a homologous oriT region with the virulence plasmid and predominantly belonged to the IncFII group, which is common in human commensal Enterobacteriaceae 50,51 . Similar findings were reported recently, showing that a bla KPC -positive IncFII plasmid sharing the nic site in the oriT with the virulence plasmid can help to mobilize the virulence plasmid from hvKp to cKp strains 49 .…”

Section: Discussionmentioning

confidence: 99%

Genomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam

Nguyen,

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Hypervirulent Klebsiella pneumoniae (hvKp) is a significant cause of severe invasive infections in Vietnam, yet data on its epidemiology, population structure and dynamics are scarce. We screened hvKp isolates from patients with bloodstream infections (BSIs) at a tertiary infectious diseases hospital in Vietnam and healthy individuals, followed by whole genome sequencing and plasmid analysis. Among 700 BSI-causing Kp strains, 100 (14.3%) were hvKp. Thirteen hvKp isolates were identified from 350 rectal swabs of healthy adults; none from 500 rectal swabs of healthy children. The hvKp isolates were genetically diverse, encompassing 17 sequence types (STs), predominantly ST23, ST86 and ST65. Among the 113 hvKp isolates, 14 (12.6%) carried at least one antimicrobial resistance (AMR) gene, largely mediated by IncFII, IncR, and IncA/C plasmids. Notably, the acquisition of AMR conjugative plasmids facilitated horizontal transfer of the non-conjugative virulence plasmid between K. pneumoniae strains. Phylogenetic analysis demonstrated hvKp isolates from BSIs and human carriage clustered together, suggesting a significant role of intestinal carriage in hvKp transmission. Enhanced surveillance is crucial to understand the factors driving intestinal carriage and hvKp transmission dynamics for informing preventive measures. Furthermore, we advocate the clinical use of our molecular assay for diagnosing hvKp infections to guide effective management.

show abstract

Section: Discussionmentioning

confidence: 99%

Genomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam

Nguyen,

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

Convergence and global epidemiology ofKlebsiella pneumoniaeplasmids harbouring theiuc3 virulence locus

Gibbon,

Couto,

Cozens

et al. 2024

Preprint

View full text Add to dashboard Cite

BackgroundKlebsiella pneumoniae(Kp) is an important pathogen of humans and animals, and recent reports of ‘convergent’ strains that carry both virulence and antimicrobial resistance genes (ARGs) have raised serious public health concern. The plasmid-borneiuclocus, encoding the siderophore aerobactin, is a key virulence factor in this species. The variantiuc3 is associated with porcine and human clinical isolates and is carried by mostly uncharacterised IncF plasmids.MethodsWe used a combination of short-read and long-read sequencing to characterise IncFIB(K)/IncFIIiuc3-carrying plasmids harboured by 79 Kp isolates and oneK. oxytocaisolate recovered as part of two large ‘One-Health’ studies in Italy (SpARK) and Thailand (OH-DART). Adding data from public repositories gave a combined dataset of 517iuc3 isolates, and the plasmids were analysed using both clustering and phylogenetic methods.FindingsWe note seven large, convergent, plasmids from Thailand that have emerged through the hybridisation of co-circulating plasmids harbouringiuc3 and antimicrobial resistance genes (ARGs) encoding extended-spectrum beta-lactamases (ESBLs). We were also able to identify putative parental plasmids which were mostly associated with two neighbouring meat markets, as were the hybrid plasmids. Clustering and global phylogenetic analyses resolved aniuc3 plasmid sub-group circulating throughout Asia, with occasional examples in Europe and elsewhere. This variant carries multiple ARGs and is commonly harboured by clinical isolates, thus warranting targeted plasmid surveillance.InterpretationOur study reveals that plasmid hybridisation leading to the convergence of resistance and virulence traits may be very common, even in non-clinical (‘One-Health’) settings. Population-scale plasmid genomics makes it possible to identify putative parental plasmids, which will help to identify plasmid types that are most likely to hybridise, and what the selective consequences may be for the plasmid and host. A distinctiuc3 plasmid sub-variant is associated with clinical isolates in Asia which requires close monitoring.Research In ContextMultiple reports of ‘convergent’ clones ofKlebsiella pneumoniaethat combine both hypervirulence and multidrug resistance (MDR-hvKp) have been published recently; a PubMed search in November 2023 using the key words ‘convergenceKlebsiella pneumoniae’ returned 143 papers, 99 of which were published from 2020 onwards. Our study demonstrates that the hybridisation of plasmids carrying AMR and virulence genes is a frequent, ongoing, process in natural populations. The subsequent transfer of plasmids conferring both traits is thus likely to be a key driver behind the spread of convergent strains. Our study also provides an exemplar of how hybrid assemblies can facilitate large-scale global genomic plasmid epidemiology.Evidence before the studyAlthough multiple recent reports highlight the emergence and spread of convergent Kp strains, the confluence of resistance and virulence genes within the same plasmid has not been studied at a population level, and putative parental plasmids are rarely identified. Moreover, there have been few high-resolution genomic epidemiology studies on closely related plasmids using both long and short-read data on a global scale.Added valueWe more than double the number of complete sequences available for plasmids harbouringiuc3 from 58 to 139 and provide evidence on the host lineages most likely to harbour these plasmids (e.g., ST35), and epidemiological source (e.g., pig, wild animal, human). Our comparative analysis of phylogenetic and clustering approaches will help to inform future plasmid epidemiological studies.ImplicationsThe hybridisation of plasmids harbouring virulence and resistance genes occurs frequently in natural populations, even within ‘One-Health’ settings. However, the selective drivers (if any) and evolutionary consequences of this phenomenon are unclear. There is clear utility in generating closed plasmid genomes on a population scale, and targeted plasmid surveillance on a clinical sub-variant ofiuc3 plasmids is warranted.

show abstract

Emergence of IS26-mediated pLVPK-like virulence and NDM-1 conjugative fusion plasmid in hypervirulent carbapenem-resistant Klebsiella pneumoniae

Cited by 2 publications

References 28 publications

Genomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam

Genomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam

Convergence and global epidemiology ofKlebsiella pneumoniaeplasmids harbouring theiuc3 virulence locus

Contact Info

Product

Resources

About