Dataset Information

An IncR Plasmid Harbored by a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Strain Possesses Five Tandem Repeats of the blaKPC-2::NTEKPC-Id Fragment.

ABSTRACT: Completed sequences of three plasmids from a carbapenem-resistant hypervirulent Klebsiella pneumoniae isolate, SH9, were obtained. In addition to the pLVPK-like virulence-conferring plasmid (pVir-CR-HvKP_SH9), the two multidrug-resistant plasmids (pKPC-CR-HvKP4_SH9 and pCTX-M-CR-HvKP4_SH9) were predicted to originate from a single pKPC-CR-HvKP4-like multireplicon plasmid through homologous recombination. Interestingly, the blaKPC-2 gene was detectable in five tandem repeats exhibiting the format of an NTEKPC-Id-like transposon (IS26-ΔTn3-ISKpn8-blaKPC-2-ΔISKpn6-korC-orf-IS26). The data suggest an important role of DNA recombination in mediating active plasmid evolution.

SUBMITTER: Dong N

PROVIDER: S-EPMC6395944 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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An IncR Plasmid Harbored by a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Strain Possesses Five Tandem Repeats of the blaKPC-2::NTEKPC-Id Fragment.

Dong Ning N Liu Lizhang L Zhang Rong R Chen Kaichao K Xie Miaomiao M Chan Edward Wai Chi EWC Chen Sheng S

Antimicrobial agents and chemotherapy 20190226 3

Completed sequences of three plasmids from a carbapenem-resistant hypervirulent Klebsiella pneumoniae isolate, SH9, were obtained. In addition to the pLVPK-like virulence-conferring plasmid (pVir-CR-HvKP_SH9), the two multidrug-resistant plasmids (pKPC-CR-HvKP4_SH9 and pCTX-M-CR-HvKP4_SH9) were predicted to originate from a single pKPC-CR-HvKP4-like multireplicon plasmid through homologous recombination. Interestingly, the blaKPC-2 gene was detectable in five tandem repe ...[more]

PMID: 30530604

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Project description:The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Egyptian hospitals has been reported. However, the genetic basis and analysis of the plasmids associated with carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) in Egypt have not been presented. Therefore, we attempted to decipher the plasmid sequences that are responsible for transferring the determinants of carbapenem resistance, particularly blaNDM-1 and blaKPC-2 Out of 34 K. pneumoniae isolates collected from two tertiary hospitals in Egypt, 31 were CRKP. Whole-genome sequencing revealed that our isolates were related to 13 different sequence types (STs). The most prevalent ST was ST101, followed by ST383 and ST11. Among the CRKP isolates, one isolate named EBSI036 has been reassessed by Nanopore sequencing. Genetic environment analysis showed that EBSI036 carried 20 antibiotic resistance genes and was identified as a CR-HvKP strain: it harbored four plasmids, namely, pEBSI036-1-NDM-VIR, pEBSI036-2-KPC, pEBSI036-3, and pEBSI036-4. The two carbapenemase genes blaNDM-1 and blaKPC-2 were located on plasmids pEBSI036-1-NDM-VIR and pEBSI036-2-KPC, respectively. The IncFIB:IncHI1B hybrid plasmid pEBSI036-1-NDM-VIR also carried some virulence factors, including the regulator of the mucoid phenotype (rmpA), the regulator of mucoid phenotype 2 (rmpA2), and aerobactin (iucABCD and iutA). Thus, we set out in this study to analyze in depth the genetic basis of the pEBSI036-1-NDM-VIR and pEBSI036-2-KPC plasmids. We report a high-risk clone ST11 KL47 serotype of a CR-HvKP strain isolated from the blood of a 60-year-old hospitalized female patient from the intensive care unit (ICU) in a tertiary care hospital in Egypt, which showed the cohabitation of a novel hybrid plasmid coharboring the blaNDM-1 and virulence genes and a blaKPC-2-carrying plasmid.IMPORTANCE CRKP has been registered in the critical priority tier by the World Health Organization and has become a significant menace to public health. The emergence of CR-HvKP is of great concern in terms of both disease and treatment. In-depth analysis of the carbapenemase-encoding and virulence plasmids may provide insight into ongoing recombination and evolution of virulence and multidrug resistance in K. pneumoniae Thus, this study serves to alert contagious disease clinicians to the presence of hypervirulence in CRKP isolates in Egyptian hospitals.

Project description:Pseudomonas aeruginosa is a major opportunistic pathogen and one of the leading bacterial species causing health care-associated infections. Carbapenems are the most effective antimicrobial agents for the treatment of severe infections caused by P. aeruginosa However, our recent surveillance demonstrated that the prevalence of carbapenem-resistant P. aeruginosa (CRPA) reached 38.67% in Zhejiang, China. By analyzing CRPA isolates collected from patients from 2006 to 2018, we found that 33% of CRPA isolates carried the gene blaKPC-2, which conferred high-level resistance to carbapenems and other β-lactams. In particular, a CRPA clone, ST463 (sequence type 463), emerged and has become the predominant CRPA clone among the population. Genome sequencing demonstrated that ST463 expansion was associated with plasmid-borne blaKPC-2 The mobile element flanking blaKPC-2, the type IV secretion system, and the successful expansion of clone ST463 might have further favored blaKPC-2 spread in P. aeruginosa Molecular clock analysis dated the emergence of clone ST463 to around 2007. Genome-wide association analysis showed that 567 genes were associated with clone ST463, including several known virulence genes related to the biosynthesis of lipooligosaccharide (LOS) O-antigens and exotoxin. These findings indicate that ST463 is expanding with plasmid-borne blaKPC-2 and virulence-related genes in nosocomial infections, and close surveillance should be undertaken in the future.IMPORTANCE Health care-associated infections, also known as nosocomial infections, are the most frequent adverse events in health care delivery worldwide, causing high rates of morbidity and mortality and high health care costs. Pseudomonas aeruginosa is one of the leading bacterial species causing health care-associated infections. Carbapenems are the most effective antimicrobial agents for the treatment of its severe infections. However, the prevalence of carbapenem-resistant P. aeruginosa (CRPA) has been increasing rapidly in recent years, and our surveillance demonstrated that the prevalence of CRPA reached 38.67% in Zhejiang, China. Genome sequencing of CRPA isolates over a decade showed that a CRPA clone (ST463) emerged recently. The clone is highly resistant to β-lactams, including carbapenems, and fluoroquinolones. Genome-wide association analysis showed that the clone expanded with virulence-related genes and the plasmid-borne carbapenem-resistant gene blaKPC-2 These findings are of significant public health importance, as the information will facilitate the control and minimization of CRPA nosocomial infections.

Project description:BackgroundCarbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) caused infections of high mortality and brought a serious impact on public health. This study aims to evaluate the epidemiology, resistance and virulence characteristics of CR-hvKP and to identify potential drivers of cross-regional transmission in different regions of China, in order to provide a basis for developing targeted prevention measures.MethodsClinical K. pneumoniae strains were collected from Jiujiang and Nanchang in Jiangxi province between November 2021 to June 2022. Clinical data of patients (age, sex, source of infection, and diagnosis) were also gathered. We characterized these strains for their genetic relatedness using PFGE, antimicrobial and virulence plasmid structures using whole-genome sequencing, and toxicity using Galleria mellonella infection model.ResultsAmong 609 strains, 45 (7.4%) CR-hvKP were identified, while the strains. isolated from Nanchang and Jiujiang accounted for 10.05% (36/358) and 3.59% (9/251). We observed that ST11-KL64 CR-hvKP had an overwhelming epidemic dominance in these two regions. Significant genetic diversity was identified among all ST11-KL64 CR-hvKP cross-regional transmission between Nanchang and Jiujiang and this diversity served as the primary driver of the dissemination of clonal groups. Virulence genes profile revealed that ST11-KL64 CR-hvKP might harbour incomplete pLVPK-like plasmids and primarily evolved from CRKP by acquiring the hypervirulence plasmid. We found the predominance of truncated-IncFIB/IncHI1B type virulence plasmids with a 25 kb fragment deletion that encoded iroBCDN clusters.ConclusionST11-KL64 is the most cross-regional prevalent type CR-hvKPs in Jiangxi province, which mainly evolved from CRKPs by acquiring a truncated-IncHI1B/IncFIB virulence plasmid with the deletion of iroBCDN. Stricter surveillance and control measures are urgently needed to prevent the epidemic transmission of ST11-KL64 CR-hvKP.

Dataset Information

An IncR Plasmid Harbored by a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae Strain Possesses Five Tandem Repeats of the blaKPC-2::NTEKPC-Id Fragment.

Publications

An IncR Plasmid Harbored by a Hypervirulent Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Strain Possesses Five Tandem Repeats of the <i>bla</i><sub>KPC-2</sub>::NTE<sub>KPC</sub>-Id Fragment.

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