Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives Evolution

BackgroundIn recent years, the emergence of multidrug resistant hypervirulent K. pneumoniae (MDR hvKp) isolates poses severe therapeutic challenge to global public health. The present study used the complete genome sequence of two MDR hvKp isolates belonging to ST23 to characterize the phylogenetic...

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Main Authors: Chaitra Shankar, Jobin John Jacob, Karthick Vasudevan, Rohit Biswas, Abi Manesh, Dhiviya Prabaa Muthuirulandi Sethuvel, Santosh Varughese, Indranil Biswas, Balaji Veeraraghavan
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2020.575289/full
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spelling doaj-c33c67c9874e4e488bcc9464ae740f602020-11-25T04:03:30ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-11-011010.3389/fcimb.2020.575289575289Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives EvolutionChaitra Shankar0Jobin John Jacob1Karthick Vasudevan2Rohit Biswas3Abi Manesh4Dhiviya Prabaa Muthuirulandi Sethuvel5Santosh Varughese6Indranil Biswas7Balaji Veeraraghavan8Department of Clinical Microbiology, Christian Medical College and Hospital, Vellore, IndiaDepartment of Clinical Microbiology, Christian Medical College and Hospital, Vellore, IndiaDepartment of Clinical Microbiology, Christian Medical College and Hospital, Vellore, IndiaCollege of Biological Sciences, University of Minnesota, Saint Paul, MN, United StatesDepartment of Infectious Diseases, Christian Medical College and Hospital, Vellore, IndiaDepartment of Clinical Microbiology, Christian Medical College and Hospital, Vellore, IndiaDepartment of Nephrology, Christian Medical College and Hospital, Vellore, IndiaDepartment of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Centre, Kansas City, KS, United StatesDepartment of Clinical Microbiology, Christian Medical College and Hospital, Vellore, IndiaBackgroundIn recent years, the emergence of multidrug resistant hypervirulent K. pneumoniae (MDR hvKp) isolates poses severe therapeutic challenge to global public health. The present study used the complete genome sequence of two MDR hvKp isolates belonging to ST23 to characterize the phylogenetic background and plasmid diversity.MethodsTwo hvKp isolates from patients with bacteremia were sequenced using Ion Torrent PGM and Oxford Nanopore MinION platforms and assembled by hybrid genome assembly approach. Comparative genomics approaches were used to investigate the population structure, evolution, virulence, and antimicrobial resistance of MDR hvKp strains.ResultsThe study isolates exhibited typical features of hvKp phenotypes associated with ST23. The convergence of multidrug resistance and hypervirulence were attributed by the presence of multiple plasmids including a 216 kb virulence plasmid and MDR plasmids belonging to IncA/C2, IncFIB, IncX3, and ColKP3 groups. The insertion of catA1 gene into virulence plasmid was observed along with genetic factors such as aerobactin, salmochelin, and rmpA2 that confer hvKp’s hypervirulent phenotype. The core genome single nucleotide polymorphism (SNP) phylogenetic analyses of the isolates showed the evolution of ST23 hvKp was predominantly driven by ICEKp acquisitions.ConclusionTo the best of our knowledge, this is the first report of MDR hvKp isolates of ST23 with insertion of catA1 gene into the virulence plasmid which presents the possibility of hotspot integration sites on the plasmids to aid acquisition of AMR genes. ST23 is no longer confined to susceptible strains of hvKp. Our findings emphasize the need for more studies on recombinant events, plasmid transmission dynamics and evolutionary process involving hvKp.https://www.frontiersin.org/articles/10.3389/fcimb.2020.575289/fullKlebsiella pneumoniaehypervirulence plasmidST23hybrid genomemultidrug resistanceOXA-232
collection DOAJ
language English
format Article
sources DOAJ
author Chaitra Shankar
Jobin John Jacob
Karthick Vasudevan
Rohit Biswas
Abi Manesh
Dhiviya Prabaa Muthuirulandi Sethuvel
Santosh Varughese
Indranil Biswas
Balaji Veeraraghavan
spellingShingle Chaitra Shankar
Jobin John Jacob
Karthick Vasudevan
Rohit Biswas
Abi Manesh
Dhiviya Prabaa Muthuirulandi Sethuvel
Santosh Varughese
Indranil Biswas
Balaji Veeraraghavan
Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives Evolution
Frontiers in Cellular and Infection Microbiology
Klebsiella pneumoniae
hypervirulence plasmid
ST23
hybrid genome
multidrug resistance
OXA-232
author_facet Chaitra Shankar
Jobin John Jacob
Karthick Vasudevan
Rohit Biswas
Abi Manesh
Dhiviya Prabaa Muthuirulandi Sethuvel
Santosh Varughese
Indranil Biswas
Balaji Veeraraghavan
author_sort Chaitra Shankar
title Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives Evolution
title_short Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives Evolution
title_full Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives Evolution
title_fullStr Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives Evolution
title_full_unstemmed Emergence of Multidrug Resistant Hypervirulent ST23 Klebsiella pneumoniae: Multidrug Resistant Plasmid Acquisition Drives Evolution
title_sort emergence of multidrug resistant hypervirulent st23 klebsiella pneumoniae: multidrug resistant plasmid acquisition drives evolution
publisher Frontiers Media S.A.
series Frontiers in Cellular and Infection Microbiology
issn 2235-2988
publishDate 2020-11-01
description BackgroundIn recent years, the emergence of multidrug resistant hypervirulent K. pneumoniae (MDR hvKp) isolates poses severe therapeutic challenge to global public health. The present study used the complete genome sequence of two MDR hvKp isolates belonging to ST23 to characterize the phylogenetic background and plasmid diversity.MethodsTwo hvKp isolates from patients with bacteremia were sequenced using Ion Torrent PGM and Oxford Nanopore MinION platforms and assembled by hybrid genome assembly approach. Comparative genomics approaches were used to investigate the population structure, evolution, virulence, and antimicrobial resistance of MDR hvKp strains.ResultsThe study isolates exhibited typical features of hvKp phenotypes associated with ST23. The convergence of multidrug resistance and hypervirulence were attributed by the presence of multiple plasmids including a 216 kb virulence plasmid and MDR plasmids belonging to IncA/C2, IncFIB, IncX3, and ColKP3 groups. The insertion of catA1 gene into virulence plasmid was observed along with genetic factors such as aerobactin, salmochelin, and rmpA2 that confer hvKp’s hypervirulent phenotype. The core genome single nucleotide polymorphism (SNP) phylogenetic analyses of the isolates showed the evolution of ST23 hvKp was predominantly driven by ICEKp acquisitions.ConclusionTo the best of our knowledge, this is the first report of MDR hvKp isolates of ST23 with insertion of catA1 gene into the virulence plasmid which presents the possibility of hotspot integration sites on the plasmids to aid acquisition of AMR genes. ST23 is no longer confined to susceptible strains of hvKp. Our findings emphasize the need for more studies on recombinant events, plasmid transmission dynamics and evolutionary process involving hvKp.
topic Klebsiella pneumoniae
hypervirulence plasmid
ST23
hybrid genome
multidrug resistance
OXA-232
url https://www.frontiersin.org/articles/10.3389/fcimb.2020.575289/full
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