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Genome sequencing and comparative analysis of an NDM-1-producing Klebsiella pneumoniae ST15 isolated from a refugee patient.

ABSTRACT: The escalating problem of antibiotic resistance, specifically cabarpenemase and extended-spectrum ?-lacatamase (ESBL) producing K. pneumoniae strains, is directly correlated with increased patient morbidity and mortality and prolonged hospitalization and costs. In this study, a comprehensive genomic analysis encompassing the resistomics, virulence repertoire and mobile genetic elements of an NDM-1 positive ESBL-producing K. pneumoniae EA-MEH ST15 isolated from a urine sample collected from a Syrian refugee was conducted. Illumina paired-end libraries were prepared and sequenced resulting in 892,300 high-quality reads. The initial assembly produced 329 contigs with a combined 5,954,825 bp and a 56.5% G+C content. Resistome analysis revealed the presence of several ?-lactamases including NDM-1, SHV-28, CTX-M-15 and OXA-1 in addition to 18 other genes encoding for resistance, among which are aph(3')-Ia, aac(6')Ib-cr, armA, strB, strA and aadA2 genes. Additionally, five plasmids IncFIB(Mar), IncHI1B, IncFIB(pKPHS1), IncFIB(K) and IncFII(K) and four integrated phages were detected. In silico MLST analysis revealed that the isolate was of sequence type ST15. To our knowledge this is the first in-depth genomic analysis of a NDM-1 positive K. pneumoniae ST15 in Lebanon associated with the recent population migration. The potential dissemination of such MDR strains is an important public health concern.

SUBMITTER: Salloum T

PROVIDER: S-EPMC5498761 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Genome sequencing and comparative analysis of an NDM-1-producing Klebsiella pneumoniae ST15 isolated from a refugee patient.

Salloum Tamara T Arabaghian Harout H Alousi Sahar S Abboud Edmond E Tokajian Sima S

Pathogens and global health 20170411 4

The escalating problem of antibiotic resistance, specifically cabarpenemase and extended-spectrum β-lacatamase (ESBL) producing K. pneumoniae strains, is directly correlated with increased patient morbidity and mortality and prolonged hospitalization and costs. In this study, a comprehensive genomic analysis encompassing the resistomics, virulence repertoire and mobile genetic elements of an NDM-1 positive ESBL-producing K. pneumoniae EA-MEH ST15 isolated from a urine sample collected from a Syr ...[more]

PMID: 28395597

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Project description:Klebsiella pneumoniae is a major cause of neonatal sepsis. Hypervirulent Klebsiella pneumoniae (hvKP) that cause invasive infections and/or carbapenem-resistant hvKP (CR-hvKP) limit therapeutic options. Such strains causing neonatal sepsis have rarely been studied. Characterization of neonatal septicemic hvKP/CR-hvKP strains in terms of resistance and virulence was carried out. Antibiotic susceptibility, molecular characterization, evaluation of clonality, in vitro virulence, and transmissibility of carbapenemase genes were evaluated. Whole-genome sequencing (WGS) and mouse lethality assays were performed on strains harboring pLVPK-associated markers. About one-fourth (26%, 28/107) of the studied strains, leading to mortality in 39% (11/28) of the infected neonates, were categorized as hvKP. hvKP-K2 was the prevalent pathotype (64.2%, 18/28), but K54 and K57 were also identified. Most strains were clonally diverse belonging to 12 sequence types, of which ST14 was most common. Majority of hvKPs possessed virulence determinants, strong biofilm-forming, and high serum resistance ability. Nine hvKPs were carbapenem-resistant, harboring blaNDM-1/blaNDM-5 on conjugative plasmids of different replicon types. Two NDM-1-producing high-risk clones, ST11 and ST15, had pLVPK-associated markers (rmpA, rmpA2, iroBCDEN, iucABCDiutA, and peg-344), of which one co-transferred the markers along with blaNDM-1. The 2 strains revealed high inter-genomic resemblance with the other hvKP reference genomes, and were lethal in mouse model. To the best of our knowledge, this study is the first to report on the NDM-1-producing hvKP ST11-K2 and ST15-K54 strains causing fatal neonatal sepsis. The presence of pLVPK-associated markers and blaNDM-1 in high-risk clones, and the co-transmission of these genes via conjugation calls for surveillance of these strains. IMPORTANCE Klebsiella pneumoniae is a leading cause of sepsis in newborns and adults. Among the 2 major pathotypes of K. pneumoniae, classical (cKP) and hypervirulent (hvKP), hvKP causes community-acquired severe fatal invasive infections in even healthy individuals, as it possesses several virulence factors. The lack of comprehensive studies on neonatal septicemic hvKPs prompted this work. Nearly 26% diverse hvKP strains were recovered possessing several resistance and virulence determinants. The majority of them exhibited strong biofilm-forming and high serum resistance ability. Nine of these strains were also carbapenem (last-resort antibiotic)-resistant, of which 2 high-risk clones (ST11-K2 and ST15-K54) harbored markers (pLVPK) noted for their virulence, and were lethal in the mouse model. Genome-level characterization of the high-risk clones showed resemblance with the other hvKP reference genomes. The presence of transmissible carbapenem-resistant gene, blaNDM, along with pLVPK-markers calls for vigilance, as most clinical microbiology laboratories do not test for them.

Dataset Information

Genome sequencing and comparative analysis of an NDM-1-producing Klebsiella pneumoniae ST15 isolated from a refugee patient.

Publications

Genome sequencing and comparative analysis of an NDM-1-producing Klebsiella pneumoniae ST15 isolated from a refugee patient.

Similar Datasets

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