Dataset Information

Mcr-1 Colistin Resistance in ESBL-Producing Klebsiella pneumoniae, France.

ABSTRACT: We report intestinal carriage of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain with high-level resistance to colistin (MIC 24 mg/L) in a patient in France who had been hospitalized for fungal meningitis. The strain had the mcr-1 plasmid gene and an inactivated mgrB gene, which are associated with colistin resistance.

SUBMITTER: Caspar Y

PROVIDER: S-EPMC5403025 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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mcr-1 Colistin Resistance in ESBL-Producing Klebsiella pneumoniae, France.

Caspar Yvan Y Maillet Mylène M Pavese Patricia P Francony Gilles G Brion Jean-Paul JP Mallaret Marie-Reine MR Bonnet Richard R Robin Frédéric F Beyrouthy Racha R Maurin Max M

Emerging infectious diseases 20170501 5

We report intestinal carriage of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain with high-level resistance to colistin (MIC 24 mg/L) in a patient in France who had been hospitalized for fungal meningitis. The strain had the mcr-1 plasmid gene and an inactivated mgrB gene, which are associated with colistin resistance. ...[more]

PMID: 28418313

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Project description:Klebsiella pneumoniae is a nosocomial pathogen with high morbidity and mortality rates in hospitalized patients. The emergence of multidrug-resistant K. pneumoniae has become more challenging to treat, with the prevalence of colistin-resistance. Therefore, reliable methods for detecting colistin resistance are required. Many plants' essential oils have antimicrobial activity and have been used to combat multiple antibiotic resistances. This study aimed to investigate the characterization and prevalence of the colistin resistance gene mcr-1 in K. pneumoniae in Egypt, evaluate rapid polymyxin NP test, determine the transferability of mcr-1 gene, and study the synergistic activity of eugenol combined with colistin against K. pneumoniae isolates. Eighty-two K. pneumonia isolates were collected from different human samples, followed by antibiotic susceptibility testing, rapid polymyxin NP test, and detection of the mcr-1 gene and its transfer frequency. Determination of the MICs of colistin alone and in combination with eugenol was performed, then mcr-1 gene expression was determined in the presence of eugenol. Thirty-two isolates (39%) were colistin-resistant. Rapid polymyxin NP test failed to detect resistant isolates with MICs below 32 µg/mL. Detection of mcr-1 gene was made in 27 (84%) of colistin resistant isolates. The rest isolates possess alteration in the mgrB gene which probably causes colistin resistance. The mcr-1 gene was transferred by conjugation to other sensitive isolates. MIC of eugenol ranged from 416 to 1664 µg/mL, and FICI ranged from 0.265 to 0.75. Results also revealed suppression of mcr-1 gene expression in the presence of sub MIC of eugenol. Our results demonstrated a high prevalence of mcr-1 in Egypt and its ability to transfer to other strains. Difficult determination of colistin-resistant isolates with low values with rapid polymyxin NP test was apparent. Eugenol exerted a synergistic effect with colistin and improved its antimicrobial activity.

Project description:In the present study, we provide the results of a detailed genomic analysis and the growth characteristics of a colistin-resistant KPC-3-producing Klebsiella pneumoniae sequence type 512 (ST512) isolate (the colR-KPC3-KP isolate) with a mutated pmrB and isogenic isolates of colR-KPC3-KP with mcr-1.2 isolated from an immunocompromised patient. From 2014 to 2017, four colR-KPC3-KP isolates were detected in rectal swab samples collected from a pediatric hematology patient at the Azienda Ospedaliero-Universitaria Pisana in Pisa, Italy. Whole-genome sequencing was performed by MiSeq sequencing (Illumina). Growth experiments were performed using different concentrations of colistin. The growth lag phases both of an isolate harboring a deletion in pmrB and of clonal variants with mcr-1.2 were assessed by the use of real-time light-scattering measurements. In the first isolate (isolate 1000-pmrBΔ, recovered in September 2014), a 17-nucleotide deletion in pmrB was detected. In subsequent isolates, the mcr-1.2 gene associated with the plasmid pIncX4-AOUP was found, while pmrB was intact. Additionally, plasmid pIncQ-AOUP, harboring aminoglycoside resistance genes, was detected. The growth curves of the first three isolates were identical without colistin exposure; however, at higher concentrations of colistin, the growth curves of the isolate with a deletion in pmrB showed longer lag phases. We observed the replacement of mutated colR-KPC3-KP pmrB by isogenic isolates with multiple resistance plasmids, including mcr-1.2-carrying pIncX4, probably due to coselection under gentamicin treatment in a patient with prolonged colR-KPC3-KP carriage. The carriage of these isolates persisted in follow-up cultures. Coselection and the advantages in growth characteristics suggest that the plasmid-mediated resistance conferred by mcr has fewer fitness costs in colR-KPC3-KP than mutations in chromosomal pmrB, contributing to the success of this highly resistant hospital-adapted epidemiological lineage.IMPORTANCE Our study shows a successful prolonged human colonization by a colistin-resistant Klebsiella pneumoniae isolate harboring mcr-1.2 An intense antibiotic therapy contributed to the maintenance of this microorganism through the acquisition of new resistance genes. The isolates carrying mcr-1.2 showed fewer fitness costs than isogenic isolates with a pmrB mutation in the chromosome. Coselection and reduced fitness costs may explain the replacement of isolates with the pmrB mutation by other isolates and the ability of the microorganism to persist despite antibiotic treatment.

Dataset Information

Mcr-1 Colistin Resistance in ESBL-Producing Klebsiella pneumoniae, France.

Publications

mcr-1 Colistin Resistance in ESBL-Producing Klebsiella pneumoniae, France.

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