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dc.contributor.authorShankar, Chaitra
dc.contributor.authorVasudevan, Karthick
dc.contributor.authorJacob, Jobin John
dc.contributor.authorBaker, Stephen
dc.contributor.authorIsaac, Barney J
dc.contributor.authorNeeravi, Ayyan Raj
dc.contributor.authorSethuvel, Dhiviya Prabaa Muthuirulandi
dc.contributor.authorGeorge, Biju
dc.contributor.authorVeeraraghavan, Balaji
dc.date.accessioned2022-05-11T19:00:11Z
dc.date.available2022-05-11T19:00:11Z
dc.date.issued2022
dc.date.submitted2022-02-13
dc.identifier.issn2235-2988
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337040
dc.description.abstractBackground: Hypervirulent variants of Klebsiella pneumoniae (HvKp) were typically associated with a broadly antimicrobial susceptible clone of sequence type (ST) 23 at the time of its emergence. Concerningly, HvKp is now also emerging within multidrug-resistant (MDR) clones, including ST11, ST15, and ST147. MDR-HvKp either carry both the virulence and resistance plasmids or carry a large hybrid plasmid coding for both virulence and resistance determinants. Here, we aimed to genetically characterize a collection of MDR-HvKp ST2096 isolates haboring hybrid plasmids carrying both antimicrobial resistance (AMR) and virulence genes. Methods: Nine K. pneumoniae ST2096 isolated over 1 year from the blood sample of hospitalized patients in southern India that were MDR and suspected to be HvKp were selected. All nine isolates were subjected to short-read whole-genome sequencing; a subset (n = 4) was additionally subjected to long-read sequencing to obtain complete genomes for characterization. Mucoviscosity assay was also performed for phenotypic assessment. Results: Among the nine isolates, seven were carbapenem-resistant, two of which carried blaNDM-5 on an IncFII plasmid and five carried blaOXA-232 on a ColKP3 plasmid. The organisms were confirmed as HvKp, with characteristic virulence genes (rmpA2, iutA, and iucABCD) carried on a large (~320 kbp) IncFIB-IncHI1B co-integrate. This hybrid plasmid also carried the aadA2, armA, blaOXA-1, msrE, mphE, sul1, and dfrA14 AMR genes in addition to the heavy-metal resistance genes. The hybrid plasmid showed about 60% similarity to the IncHI1B virulence plasmid of K. pneumoniae SGH10 and ~70% sequence identity with the first identified IncHI1B pNDM-MAR plasmid. Notably, the hybrid plasmid carried its type IV-A3 CRISPR-Cas system which harbored spacer regions against traL of IncF plasmids, thereby preventing their acquisition. Conclusion: The convergence of virulence and AMR is clinically concerning in K. pneumoniae. Our data highlight the role of hybrid plasmids carrying both AMR and virulence genes in K. pneumoniae ST2096, suggesting that MDR-HvKp is not confined to selected clones; we highlight the continued emergence of such genotypes across the species. The convergence is occurring globally amidst several clones and is of great concern to public health.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectCellular and Infection Microbiology
dc.subjecthypervirulent
dc.subjectK. pneumoniae
dc.subjectST2096
dc.subjecthybrid plasmid
dc.subjectCRISPR-Cas
dc.subjectmultidrug resistance
dc.titleHybrid Plasmids Encoding Antimicrobial Resistance and Virulence Traits Among Hypervirulent Klebsiella pneumoniae ST2096 in India.
dc.typeArticle
dc.date.updated2022-05-11T19:00:10Z
prism.publicationNameFront Cell Infect Microbiol
prism.volume12
dc.identifier.doi10.17863/CAM.84463
dcterms.dateAccepted2022-03-21
rioxxterms.versionofrecord10.3389/fcimb.2022.875116
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBaker, Stephen [0000-0003-1308-5755]
dc.identifier.eissn2235-2988
cam.issuedOnline2022-04-27


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