Dataset Information

Resistome Profiles, Plasmid Typing, and Whole-Genome Phylogenetic Tree Analyses of BlaNDM-9 and Mcr-1 Co-Harboring Escherichia coli ST617 from a Patient without a History of Farm Exposure in Korea.

ABSTRACT: Recently, a blaNDM-9 and mcr-1 co-harboring E. coli ST 617 isolate was identified from an asymptomatic carrier in Korea. An 81-year-old female was admitted to a university hospital for aortic cardiac valve repair surgery. Following surgery, she was admitted to the intensive care unit (ICU) for three days, and carbapenem-resistant E. coli YMC/2017/02/MS631 was isolated from a surveillance culture (rectal swab). Antimicrobial susceptibility testing (AST) for colistin was not performed at that time. Upon retrospective study, further AST revealed resistance to all tested antibiotics, including meropenem, imipenem, ceftazidime-avibactam, amikacin, gentamicin, ciprofloxacin, trimethoprim-sulfamethoxazole, and colistin, with the exception of tigecycline. Whole genome sequencing analyses showed that this strain belonged to the ST617 serotype O89/162: H10 and harbored three ?-lactamase genes (blaTEM-1B, blaCTX-M-55, blaNDM-9), mcr-1, and 14 other resistance genes. Seven plasmid replicon types (IncB, IncFII, IncI2, IncN, IncY, IncR, IncX1) were identified. Horizontal transfer of blaNDM-9 and mcr-1 from donor cells to the recipient E. coli J53 has been observed. blaNDM-9 and mcr-1 were carried by IncB and IncI2 plasmids, respectively. To speculate on the incidence of this strain, routine rectal swab screening to identify asymptomatic carriers might be warranted, in addition to the screening of ICU patients.

SUBMITTER: Nguyen LP

PROVIDER: S-EPMC6963575 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Resistome Profiles, Plasmid Typing, and Whole-Genome Phylogenetic Tree Analyses of BlaNDM-9 and Mcr-1 Co-Harboring Escherichia coli ST617 from a Patient without a History of Farm Exposure in Korea.

Nguyen Le Phuong LP Pinto Naina Adren NA Vu Thao Nguyen TN Mai Hung H Pham An Ht AH Lee Hyunsook H Cho Young Lag YL Byun Jung-Hyun JH D'Souza Roshan R Yong Dongeun D

Pathogens (Basel, Switzerland) 20191031 4

Recently, a blaNDM-9 and mcr-1 co-harboring E. coli ST 617 isolate was identified from an asymptomatic carrier in Korea. An 81-year-old female was admitted to a university hospital for aortic cardiac valve repair surgery. Following surgery, she was admitted to the intensive care unit (ICU) for three days, and carbapenem-resistant E. coli YMC/2017/02/MS631 was isolated from a surveillance culture (rectal swab). Antimicrobial susceptibility testing (AST) for ...[more]

PMID: 31683614

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Project description:The rapid increase of carbapenem resistance in Gram-negative bacteria has resurrected the importance of the polymyxin antibiotics. The recent discovery of plasmid-mediated polymyxin resistance (mcr-1) in carbapenem-resistant Enterobacteriaceae serves as an important indicator that the golden era of antibiotics is under serious threat. We assessed the bacterial killing of 15 different FDA-approved antibiotics alone and in combination with polymyxin B in time-killing experiments against Escherichia coli MCR1_NJ, the first reported isolate in the United States to coharbor mcr-1 and a New Delhi metallo-β-lactamase gene (blaNDM-5). The most promising regimens were advanced to the hollow-fiber infection model (HFIM), where human pharmacokinetics for polymyxin B, aztreonam, and amikacin were simulated over 240 h. Exposure to polymyxin B monotherapy was accompanied by MCR1_NJ regrowth but not resistance amplification (polymyxin B MIC from 0 to 240 h [MIC0h to MIC240h] of 4 mg/liter), whereas amikacin monotherapy caused regrowth and simultaneous resistance amplification (amikacin MIC0h of 4 mg/liter versus MIC240h of >64 mg/liter). No MCR1_NJ colonies were observed for any of the aztreonam-containing regimens after 72 h. However, HFIM cartridges for both aztreonam monotherapy and the polymyxin B-plus-aztreonam regimen were remarkably turbid, and the presence of long, filamentous MCR1_NJ cells was evident in scanning electron microscopy, suggestive of a nonreplicating persister (NRP) phenotype. In contrast, the 3-drug combination of polymyxin B, aztreonam, and amikacin provided complete eradication (>8-log10 CFU/ml reduction) with suppression of resistance and prevention of NRP formation. This is the first comprehensive pharmacokinetic/pharmacodynamic study to evaluate triple-drug combinations for polymyxin- and carbapenem-resistant E. coli coproducing MCR-1 and NDM-5 and will aid in the preparation for a so-called "postantibiotic" era.IMPORTANCE A global health crisis may be on the horizon, as the golden era of antibiotics is under serious threat. We recently reported the first case in the United States of a highly resistant, Escherichia coli so-called "superbug" (MCR1_NJ), coharboring two of the most worrying antibiotic resistance genes, encoding mobile colistin resistance (mcr-1) and a New Delhi metallo-β-lactamase (blaNDM-5). Worryingly, the medical community is vulnerable to this emerging bacterial threat because optimal treatment strategies are undefined. Here, we report the activity of an optimized combination using simulated human doses of commercially available antibiotics against MCR1_NJ. A unique triple combination involving a cocktail of polymyxin B, aztreonam, and amikacin eradicated the MCR-1- and NDM-5-producing E. coli Each antimicrobial agent administered as monotherapy or in double combinations failed to eradicate MCR1_NJ at a high inoculum. To our knowledge, this is the first study to propose 3-drug therapeutic solutions against superbugs coharboring mcr-1 and blaNDM, seeking to prepare clinicians for future occurrences of these pathogens.

Project description:The plasmid-mediated transmission of antibiotic resistance genes has been reported to be involved in the development of antibiotic resistance in bacteria, and poses a serious threat for the success of bacterial infection treatment and human health worldwide. The present study used a 454 GS‑FLX pyrosequencing system to determine the ~140 kb nucleotide sequence of plasmid pHS36‑NDM, which was identified in a Salmonella Stanley isolate from the stool sample of an 11‑month‑old girl at Lishui Central Hospital, China, and which contains a New Delhi metallo‑β‑lactamase‑1 (NDM‑1) carbapenem resistance gene (blaNDM‑1). The 181 open reading frames encode proteins with functions including replication, stable inheritance, antibiotic resistance and mobile genetic elements. Both horizontal transfer and passage stability‑related genes were identified in pHS36‑NDM, including a conserved type 4 secretion system and stbA (stable plasmid inheritance protein A). Two multidrug resistance gene islands were identified: The ISEcp1‑blaCMY transposition unit which contains a CMY‑6 β‑lactamase gene (blaCMY‑6) and a quaternary ammonium compound resistance gene (sugE); and the intI1‑ISCR27 accessory region, which contained a trimethoprim resistance gene (dfrA12), two aminoglycoside resistance genes (aadA2 and rmtC), a truncated quaternary ammonium compound resistance gene (qacE∆1), a sulfonamide resistance gene (sul1), the blaNDM‑1 carbapenemase and a bleomycin resistance gene (bleMBL). pHS36‑NDM shared high homology with other blaNDM‑1‑containing plasmids reported in Sweden, Italy and Japan. However, no previous international travel history was documented for the patient and her family, even to neighboring cities. Furthermore, pHS36‑NDM is of a different incompatibility group to other published blaNDM‑1‑carrying plasmids reported in China, with low homology in the surrounding structure of blaNDM‑1. The present study will facilitate the understanding of the underlying resistance and dispersal mechanism of pHS36‑NDM, and will deepen our recognition of the ongoing spread of the blaNDM‑1‑containing plasmids.

Project description:The prevalence and transmission of mobile colistin resistance (mcr) genes have led to a severe threat to humans and animals. Escherichia fergusonii is an emerging pathogen which is closely related to a variety of diseases. However, the report of mcr genes harboring E. fergusonii is still rare. One study in Brazil reported the E. fergusonii isolates with IncHI2-type plasmids harboring mcr-1. A Chinese study reported two strains carrying mcr-1 gene with the same plasmid type IncI2. Here, we identified two strains of E. fergusonii carrying mcr-1 gene from farm environments with IncX4-type and IncI2-type plasmids, respectively. To our best knowledge, this is the first report about mcr-1 gene located on IncX4-type plasmid in E. fergusonii. We investigate the resistance mechanism of colistin-resistant Escherichia fergusonii strains 6S41-1 and 5ZF15-2-1 and elucidate the genetic context of plasmids carrying mcr-1 genes. In addition, we also investigated chromosomal mutations mediated colistin resistance in these two strains. Species identification was performed using MALDI-TOF MS and 16S rRNA gene sequencing. The detection of mcr-1 gene was determined by PCR and Sanger sequencing. S1-pulsed-field gel electrophoresis (PFGE), Southern blotting, antimicrobial susceptibility testing, conjugation experiments, complete genome sequencing, and core genome analysis were conducted to investigate the characteristics of isolates harboring mcr-1. The mcr-1 genes on two strains were both plasmids encoded and the typical IS26-parA-mcr-1-pap2 cassette was identified in p6S41-1 while a nikA-nikB-mcr-1 locus sites on the conjugative plasmid p5ZF15-2-1. In addition, Core genome analysis reveals that E. fergusonii 6S41-1 and 5ZF15-2-1 have close genetic relationships. The mcr-1 gene is located on conjugative IncI2-type plasmid p5ZF15-2-1, which provides support for its further transmission. In addition, there's the possibility of mcr-1 spreading to humans through farm environments and thereby threatening public health. Therefore, continuous monitoring and investigations of mcr-1 among Enterobacteriaceae in farm environments are necessary to control the spread.

Dataset Information

Resistome Profiles, Plasmid Typing, and Whole-Genome Phylogenetic Tree Analyses of BlaNDM-9 and Mcr-1 Co-Harboring Escherichia coli ST617 from a Patient without a History of Farm Exposure in Korea.

Publications

Resistome Profiles, Plasmid Typing, and Whole-Genome Phylogenetic Tree Analyses of <i>Bla</i><sub>NDM-9</sub> and <i>Mcr-1</i> Co-Harboring <i>Escherichia coli</i> ST617 from a Patient without a History of Farm Exposure in Korea.

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