Dataset Information

Characterization of a carbapenem- and colistin-resistant Enterobacter cloacae carrying Tn6901 in bla NDM-1 genomic context.

ABSTRACT: We report a clinical strain of Enterobacter cloacae, PIMB10EC27, isolated in Vietnam in 2010 that was resistant to 21 of 26 tested antibiotics, including carbapenems (MICs >64 µg/mL) and colistin (MIC >128 µg/mL). The complete genome of strain PIMB10EC27 was sequenced by PacBio RSII and the Illumina Miseq system. Whole-genome analysis revealed that PIMB10EC27 contains a chromosome of the ST513 group (PIMBEC27, length 5,272,177 bp) and two plasmids, pEC27-1 of the IncX3 group (length 62,470 bp) and pEC27-2 of the IncHI1 group (length 84,602 bp). It also revealed that strain PIMB10EC27 carries 15 genes that confer resistance to at least 10 antibiotic groups. Particularly, the insertion of ISKpn19 and Tn6901 into the genomic context of bla NDM-1 was first identified and described. In another context, amino acid mutations G273D in PmrB and F515S in PmrC were first identified on the chromosome of PIMB10EC27, which may confer resistance to colistin in this strain.

SUBMITTER: Le-Ha TD

PROVIDER: S-EPMC6498974 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Characterization of a carbapenem- and colistin-resistant Enterobacter cloacae carrying Tn6901 in bla NDM-1 genomic context.

Le-Ha Tam-Duong TD Le Lien L Le-Vo Hong-Ngoc HN Anda Mizue M Motooka Daisuke D Nakamura Shota S Tran Linh Khanh LK Tran Phuong Thi-Bich PT Iida Tetsuya T Cao Van V

Infection and drug resistance 20190403

We report a clinical strain of Enterobacter cloacae, PIMB10EC27, isolated in Vietnam in 2010 that was resistant to 21 of 26 tested antibiotics, including carbapenems (MICs >64 µg/mL) and colistin (MIC >128 µg/mL). The complete genome of strain PIMB10EC27 was sequenced by PacBio RSII and the Illumina Miseq system. Whole-genome analysis revealed that PIMB10EC27 contains a chromosome of the ST513 group (PIMBEC27, length 5,272,177 bp) and two plasmids, pEC27-1 of the IncX3 group (length 62,47 ...[more]

PMID: 31118694

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Project description:Recent reports have established the escalating threat of carbapenem-resistant Enterobacter cloacae complex (CREC). Here, we demonstrate that CREC has evolved as a highly antibiotic-resistant rather than highly virulent nosocomial pathogen. Applying genomics and Bayesian phylogenetic analyses to a 7-year collection of CREC isolates from a northern Manhattan hospital system and to a large set of publicly available, geographically diverse genomes, we demonstrate clonal spread of a single clone, ST171. We estimate that two major clades of epidemic ST171 diverged prior to 1962, subsequently spreading in parallel from the Northeastern to the Mid-Atlantic and Midwestern United States and demonstrating links to international sites. Acquisition of carbapenem and fluoroquinolone resistance determinants by both clades preceded widespread use of these drugs in the mid-1980s, suggesting that antibiotic pressure contributed substantially to its spread. Despite a unique mobile repertoire, ST171 isolates showed decreased virulence in vitro While a second clone, ST78, substantially contributed to the emergence of CREC, it encompasses diverse carbapenemase-harboring plasmids, including a potentially hypertransmissible IncN plasmid, also present in other sequence types. Rather than heightened virulence, CREC demonstrates lineage-specific, multifactorial adaptations to nosocomial environments coupled with a unique potential to acquire and disseminate carbapenem resistance genes. These findings indicate a need for robust surveillance efforts that are attentive to the potential for local and international spread of high-risk CREC clones.IMPORTANCE Carbapenem-resistant Enterobacter cloacae complex (CREC) has emerged as a formidable nosocomial pathogen. While sporadic acquisition of plasmid-encoded carbapenemases has been implicated as a major driver of CREC, ST171 and ST78 clones demonstrate epidemic potential. However, a lack of reliable genomic references and rigorous statistical analyses has left many gaps in knowledge regarding the phylogenetic context and evolutionary pathways of successful CREC. Our reconstruction of recent ST171 and ST78 evolution represents a significant addition to current understanding of CREC and the directionality of its spread from the Eastern United States to the northern Midwestern United States with links to international collections. Our results indicate that the remarkable ability of E. cloacae to acquire and disseminate cross-class antibiotic resistance rather than virulence determinants, coupled with its ability to adapt under conditions of antibiotic pressure, likely led to the wide dissemination of CREC.

Project description:IntroductionColistin is regarded as one of the last-resort antibiotics against severe infections caused by carbapenem-resistant Enterobacteriaceae. Strains with cooccurrence of mcr-9 and carbapenemase genes are of particular concern. This study aimed to investigate the genetic characteristics of a bla KPC-2-carrying plasmid, bla NDM-1-carrying plasmid and mcr-9-carrying plasmid coexisting in a carbapenem-resistant Enterobacter hormaechei isolate.MethodsE. hormaechei strain E1532 was subjected to whole-genome sequencing, and the complete nucleotide sequences of three resistance plasmids identified in the strain were compared with related plasmid sequences. The resistance phenotypes mediated by these plasmids were analyzed by plasmid transfer, carbapenemase activity and antimicrobial susceptibility testing.ResultsWhole-genome sequencing revealed that strain E1532 carries three different resistance plasmids, pE1532-KPC, pE1532-NDM and pE1532-MCR. pE1532-KPC harboring bla KPC-2 and pE1532-NDM harboring bla NDM-1 are highly identical to the IncR plasmid pHN84KPC and IncX3 plasmid pNDM-HN380, respectively. The mcr-9-carrying plasmid pE1532-MCR possesses a backbone highly similar to that of the IncHI2 plasmids R478 and p505108-MDR, though their accessory modules differ. These three coexisting plasmids carry a large number of resistance genes and contribute to high resistance to almost all antibiotics tested, except for amikacin, trimethoprim/sulfamethoxazole, tigecycline and polymyxin B. Most of the plasmid-mediated resistance genes are located in or flanked by various mobile genetic elements, facilitating horizontal transfer of antibiotic resistance genes.DiscussionThis is the first report of a single E. hormaechei isolate with coexistence of three resistance plasmids carrying mcr-9 and the two most common carbapenemase genes, bla KPC-2 and bla NDM-1. The prevalence and genetic features of these coexisting plasmids should be monitored to facilitate the establishment of effective strategies to control their further spread.

Dataset Information

Characterization of a carbapenem- and colistin-resistant Enterobacter cloacae carrying Tn6901 in bla NDM-1 genomic context.

Publications

Characterization of a carbapenem- and colistin-resistant <i>Enterobacter cloacae</i> carrying Tn<i>6901</i> in <i>bla</i> <sub>NDM-1</sub> genomic context.

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