Dataset Information

ICEKp2: description of an integrative and conjugative element in Klebsiella pneumoniae, co-occurring and interacting with ICEKp1.

ABSTRACT: Klebsiella pneumoniae is a human pathogen, prominent in antimicrobial-resistant and nosocomial infection. The integrative and conjugative element ICEKp1 is present in a third of clinical isolates and more prevalent in invasive disease; it provides genetic diversity and enables the spread of virulence-associated genes. We report a second integrative conjugative element that can co-occur with ICEKp1 in K. pneumoniae. This element, ICEKp2, is similar to the Pseudomonas aeruginosa pathogenicity island PAPI. We identified ICEKp2 in K. pneumoniae sequence types ST11, ST258 and ST512, which are associated with carbapenem-resistant outbreaks in China and the US, including isolates with and without ICEKp1. ICEKp2 was competent for excision, but self-mobilisation to recipient Escherichia coli was not detected. In an isolate with both elements, ICEKp2 positively influenced the efficiency of plasmid mobilisation driven by ICEKp1. We propose a putative mechanism, in which a Mob2 ATPase of ICEKp2 may contribute to the ICEKp1 conjugation machinery. Supporting this mechanism, mob2, but not a variant with mutations in the ATPase motif, restored transfer efficiency to an ICEKp2 knockout. This is the first demonstration of the interaction between integrative and conjugative genetic elements in a single Gram-negative bacterium with implications for understanding evolution by horizontal gene transfer.

SUBMITTER: Farzand R

PROVIDER: S-EPMC6761156 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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ICEKp2: description of an integrative and conjugative element in Klebsiella pneumoniae, co-occurring and interacting with ICEKp1.

Farzand Robeena R Rajakumar Kumar K Zamudio Roxana R Oggioni Marco R MR Barer Michael R MR O'Hare Helen M HM

Scientific reports 20190925 1

Klebsiella pneumoniae is a human pathogen, prominent in antimicrobial-resistant and nosocomial infection. The integrative and conjugative element ICEKp1 is present in a third of clinical isolates and more prevalent in invasive disease; it provides genetic diversity and enables the spread of virulence-associated genes. We report a second integrative conjugative element that can co-occur with ICEKp1 in K. pneumoniae. This element, ICEKp2, is similar to the Pseudomonas aeruginosa pathogenicity isla ...[more]

PMID: 31554924

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Project description:BackgroundDissemination of antimicrobial resistance genes has become an important public health and biodefense threat. Plasmids are important contributors to the rapid acquisition of antibiotic resistance by pathogenic bacteria.Principal findingsThe nucleotide sequence of the Klebsiella pneumoniae multiresistance plasmid pMET1 comprises 41,723 bp and includes Tn1331.2, a transposon that carries the bla(TEM-1) gene and a perfect duplication of a 3-kbp region including the aac(6')-Ib, aadA1, and bla(OXA-9) genes. The replication region of pMET1 has been identified. Replication is independent of DNA polymerase I, and the replication region is highly related to that of the cryptic Yersinia pestis 91001 plasmid pCRY. The potential partition region has the general organization known as the parFG locus. The self-transmissible pMET1 plasmid includes a type IV secretion system consisting of proteins that make up the mating pair formation complex (Mpf) and the DNA transfer (Dtr) system. The Mpf is highly related to those in the plasmid pCRY, the mobilizable high-pathogenicity island from E. coli ECOR31 (HPI(ECOR31)), which has been proposed to be an integrative conjugative element (ICE) progenitor of high-pathogenicity islands in other Enterobacteriaceae including Yersinia species, and ICE(Kp1), an ICE found in a K. pneumoniae strain causing primary liver abscess. The Dtr MobB and MobC proteins are highly related to those of pCRY, but the endonuclease is related to that of plasmid pK245 and has no significant homology with the protein of similar function in pCRY. The region upstream of mobB includes the putative oriT and shares 90% identity with the same region in the HPI(ECOR31).ConclusionsThe comparative analyses of pMET1 with pCRY, HPI(ECOR31), and ICE(Kp1 )show a very active rate of genetic exchanges between Enterobacteriaceae including Yersinia species, which represents a high public health and biodefense threat due to transfer of multiple resistance genes to pathogenic Yersinia strains.

Project description:The higher resistance rate to ceftazidime-avibactam (CZA) is mainly related to carbapenem resistance, especially New Delhi metallo-β-lactamase (NDM). The CZA-susceptible Klebsiella pneumoniae (K191663) and the later CZA-resistant isolates (K191724, K191725, K191773) co-producing NDM-4 and OXA-181 were obtained from the same hospitalized patient returning from Vietnam. Our study aims to elucidate the diversity of K. pneumoniae ST16 through comparative analysis of whole-genome sequencing (WGS) data and identify the potential evolution of plasmids by sequencing longitudinal clinical isolates during antibiotic treatment. Firstly, multilocus sequence typing analysis and phylogenic analysis suggested that these strains belong to the two lineages of K. pneumoniae ST16. Surprisingly, the CZA-resistant strains were closely related to K. pneumoniae ST16 described in South Korea, instead of the blaNDM-4- or blaOXA-181-carrying ST16 reported in Vietnam. Secondly, blaNDM-4, blaTEM-1B, and rmtB co-existed on a self-conjugative IncFII(Yp)-like plasmid, which played a significant role in CZA resistance. It could transfer into the recipient Escherichia coli J53 at high frequency, indicating the risk of mobile carbapenemases. In addition, the loss of 12-kbp fragment occurred in blaNDM-4-positive isolate (K191773), which was likely caused by insertion sequence-mediated homologous recombination. Last but not least, as a repressor of acrAB operon system, acrR was truncated by a frameshift mutation in K191663. Thus, our study provided baseline information for monitoring the occurrence and development of bacterial resistance. IMPORTANCE As a leading health care-acquired infection pathogen, Klebsiella pneumoniae is threatening a large number of inpatients due to its diverse antibiotic resistance and virulence factors. Heretofore, with a growing number of reports about the coexistence of several carbapenemases in carbapenem-resistant K. pneumoniae (CRKP), epidemiologic surveillance has been strengthened. Nevertheless, the nosocomial outbreaks by CRKP ST16 are gradually increasing worldwide. Our study provides a deeper insight into the diversification of clinical isolates of CRKP ST16 in China. In addition, the comparison analysis of resistant plasmids may reveal the transmission of carbapenemase-encoding genes. Furthermore, our study also highlights the importance of longitudinal specimen collection and continuous monitoring during the treatment, which play a crucial role in understanding the development of antibiotic resistance and the evolution of resistance plasmids.

Dataset Information

ICEKp2: description of an integrative and conjugative element in Klebsiella pneumoniae, co-occurring and interacting with ICEKp1.

Publications

ICEKp2: description of an integrative and conjugative element in Klebsiella pneumoniae, co-occurring and interacting with ICEKp1.

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