Genomic surveillance framework and global population structure for<i>Klebsiella pneumoniae</i>

Mmc, Lam; Rr, Wick; Kl, Wyres; Holt, Kathryn E.

doi:10.1101/2020.12.14.422303

Cited by 35 publications

(34 citation statements)

References 76 publications

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“…Known resistance and virulence loci are identified in Pathogenwatch via Kleborate [28]. Resistance mechanisms currently include SNPs, acquired genes, and gene truncations that are relevant for different antibiotics or antibiotic classes.…”

Section: Resultsmentioning

confidence: 99%

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Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch

Argimón¹,

David²,

Underwood³

et al. 2021

Preprint

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Background: Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting. Methods: We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16,537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1,636 genomes from four low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR. Results: Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (e.g. ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae, which represent possible vaccine candidates, showed that three O-types (O1-O3) represented 88.9% of all genomes, whereas capsule types were much more diverse. Conclusions: Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance.

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Section: Resultsmentioning

confidence: 99%

“…The Speciator tool assigns species by comparing assemblies to genomes within a reference library via Mash [26, 27]. This library comprises a manually curated set of reference assemblies tailored for Klebsiella and other Enterobacteriaceae species from Kleborate (currently v. 2.0.1) [28].…”

Section: Methodsmentioning

confidence: 99%

Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch

Argimón¹,

David²,

Underwood³

et al. 2021

Preprint

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“…Multilocus sequence typing (MLST, 7 genes) was performed using the Institut Pasteur Klebsiella MLST (Diancourt et al, 2005) database (https://bigsdb.pasteur.fr/klebsiella/). Kleborate (Lam et al, 2020) and BIGSdb analytical tools (https://bigsdb.pasteur.fr/klebsiella/) (Jolley et al, 2018) were used to define the presence of antimicrobial resistance, heavy metal tolerance, virulence genes and to characterize the capsular gene cluster . Geneious Prime 2019.1.1 software (https://www.geneious.com) was used for further manual curation of antibiotic resistance genes, and ISFinder (https://isfinder.biotoul.fr) was used to look for the insertion sequences in the resistance genes or in their genetic context.…”

Section: Mlst and Genomic Analyses Of Resistance Virulence And Other Genetic Elementsmentioning

confidence: 99%

Genomic evolution of the globally disseminated multidrug-resistantKlebsiella pneumoniaeclonal group 147

Rodrigues

Desai

Passet

et al. 2021

Preprint

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Background: The rapid emergence of multidrug-resistant Klebsiella pneumoniae (Kp) is largely driven by the spread of specific clonal groups (CG). Of these, CG147 includes 7-gene MLST sequence types ST147, ST273 and ST392. CG147 has caused nosocomial outbreaks across the world, but its global population dynamics remain unknown. Here, we report a pandrug-resistant ST147 clinical isolate from India (strain DJ) and define the evolution and global emergence of CG147. Methods: Antimicrobial susceptibility testing (EUCAST guidelines) and genome sequencing (Illumina and Oxford Nanopore technologies, Unicycler assembly) were performed on strain DJ. Additionally, we collated 217 publicly available CG147 genomes (NCBI, May 2019). CG147 evolution was inferred within a temporal phylogenetic framework (BEAST) based on a recombination-free sequence alignment (Roary/Gubbins). Comparative genomic analyses focused on resistance and virulence genes and other genetic elements (BIGSdb, Kleborate, PlasmidFinder, PHASTER, ICEFinder and CRISPRCasFinder). Results: Strain DJ had a pandrug resistance phenotype. Its genome comprised 7 plasmids and 1 linear phage-plasmid. Four carbapenemase genes were detected: blaNDM-5 and 2 copies of blaOXA-181 in the chromosome, and a second copy of blaNDM-5 on an 84 kb IncFII plasmid. CG147 genomes carried a mean of 13 acquired resistance genes or mutations; 63% carried a carbapenemase gene and 83% harbored blaCTX-M. All CG147 genomes presented GyrA and ParC mutations and a common subtype IV-E CRISPR-Cas system. ST392 and ST273 emerged in 2005 and 1995, respectively. ST147, the most represented phylogenetic branch, was itself divided into two main clades with distinct capsular loci: KL64 (74%, DJ included, emerged in 1994 and disseminated worldwide, with carbapenemases varying among world regions) and KL10 (20%, 2002, predominantly found in Asian countries, associated with carbapenemases NDM and OXA-48-like). Further, subclades within ST147-KL64 differed in the yersiniabactin locus, OmpK35/K36 mutations, plasmid replicons and prophages. The absence of IncF plasmids in some subclades was associated with a possible activity of a CRISPR-Cas system. Conclusions: K. pneumoniae clonal group CG147 comprises pandrug- or extensively-resistant isolates and carries multiple and diverse resistance genes and mobile genetic elements, including chromosomal blaNDM-5. Its emergence is driven by the spread of several phylogenetic clades marked by their own genomic features and specific temporo-spatial dynamics. These findings highlight the need for precision surveillance strategies to limit the spread of particularly concerning CG147 subsets.

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“…Additional AMR determinants, virulence factors, and typing (K-locus, wzi, and O-locus) were detected and species predicted using Kleborate, and Kaptive as implemented on the PathogenWatch platform (https://pathogen.watch) [20,21]. SNP variants were called relative to a reference genome (K. pneumoniae strain K2044 (NCBI RefSeq NZ_CP026011.1)) and a maximum likelihood phylogeny inferred from pseudogenome alignment of the variants using IQ_TREE with GTR+G model and 1000 bootstrap replicates [19,22].…”

Section: Quality Control and Bioinformatic Analysismentioning

confidence: 99%

Complexity of Genomic Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Colombia Urges the Reinforcement of Whole Genome Sequencing-Based Surveillance Programs

Saavedra

Bernal

Montilla-Escudero

et al. 2021

Preprint

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Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging public health problem. This study explores the specifics of CRKP epidemiology in Colombia based on whole genome sequencing (WGS) of the National Reference Laboratory at Instituto Nacional de Salud (INS)′s 2013-2017 sample collection. Methods: A total of 425 CRKP isolates from 21 departments were analyzed by HiSeq-X10®Illumina high-throughput sequencing. Bioinformatic analysis was performed, primarily using the pipelines developed collaboratively by the National Institute for Health Research Global Health Research Unit (GHRU) on Genomic Surveillance of AMR, and AGROSAVIA. Results: Of the 425 CRKP isolates, 91.5% were carbapenemase-producing strains. The data support a recent expansion and the endemicity of CRKP in Colombia with the circulation of 7 high-risk clones, the most frequent being CG258 (48.39% of isolates). We identified genes encoding carbapenemases blaKPC-3, blaKPC-2, blaNDM-1, blaNDM-9, blaVIM-2, blaVIM-4, and blaVIM-24, and various mobile genetic elements (MGE). The virulence of CRKP isolates was low, but colibactin (clb3) was present in 25.2% of isolates, and a hypervirulent CRKP clone (CG380) was reported for the first time in Colombia. ST258, ST512, and ST4851 were characterized by low levels of diversity in the core genome (ANI > 99.9%). Conclusions: The study outlines complex CRKP epidemiology in Colombia. CG258 expanded clonally and carries specific carbapenemases in specific MGEs, while the other high-risk clones (CG147, CG307, and CG152) present a more diverse complement of carbapenemases. The specifics of the Colombian situation stress the importance of WGS-based surveillance to monitor evolutionary trends of STs, MGE, and resistance and virulence genes.

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Genomic surveillance framework and global population structure forKlebsiella pneumoniae

Cited by 35 publications

References 76 publications

Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch

Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch

Genomic evolution of the globally disseminated multidrug-resistantKlebsiella pneumoniaeclonal group 147

Complexity of Genomic Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Isolates in Colombia Urges the Reinforcement of Whole Genome Sequencing-Based Surveillance Programs

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