Etats-Unis : découverte d'une super-bactérie résistante à tous les antibiotiques

Description

Antimicrobial Agents and Chemotherapy

Sujets

• Antibiotique
• Bacteria
• Résistance
• Recherche (homonymie)

Informations

• Publié par: Fil_actu
• Publié le: 27 mai 2016
• Nombre de lectures: 3
• Langue: English

Extrait

Kurt E. Schaecher

#Alternative corresponding author

Bethesda, Maryland, USA

Email:[e-mail]

Walter Reed Army Institute of Research, 2S35

mcr1in the USA

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Running Title:Colistin resistance in the USA

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1 1 2 1 3# Clifford , Mary Hinkle , Timothy Whitman , Emil Lesho , and Kurt E. Schaecher

1#* 1* 1 1 1 Patrick McGann , Erik Snesrud , Rosslyn Maybank , Brendan Corey , Ana C. Ong , Robert

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# Corresponding author

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Escherichia coliHarboringmcr1andbla CTX-M on a Novel IncF Plasmid: First report of

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AAC Accepted Manuscript Posted Online 26 May 2016 Antimicrob. Agents Chemother. doi:10.1128/AAC.01103-16 Copyright © 2016 McGann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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Department of Pathology,

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1 Multidrug-resistant Organism Repository and Surveillance Network, Walter Reed Army

Walter Reed National Military Medical Center

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*PMG and ES contributed equally to this manuscript

Patrick Mc Gann, PhD

Email:[e-mail]

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Institute of Research, Silver Spring, Maryland, USA.

2 Department of Infectious Diseases, Walter Reed National Military Medical Center, MD, USA .

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Silver Spring, Maryland 20910, USA

Phone: [phone]

3 Department of Pathology, Walter Reed National Military Medical Center, MD, USA.

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The recent discovery of a plasmid-borne colistin resistance gene,mcr1, heralds the emergence

of truly pan-drug resistant bacteria (1). The gene has been found primarily inEscherichia coli,

but has also been identified in other members of theEnterobacteriaceaefrom human, animal,

food and environmental samples on every continent (2-5). In response to this threat, starting in

May 2016, all extended-spectrum β-lactamase (ESBL)-producingE.coliclinical isolates

submitted to the clinical microbiology laboratory at the Walter Reed National Military Medical

Center (WRNMMC) were tested for resistance to colistin by E-test. Herein we report the

presence ofmcr1in anE. colicultured from a patient with a urinary tract infection (UTI) in the

United States.

E. coliMRSN 388634 was cultured from the urine of a 49 year-old female who presented to a

th clinic in Pennsylvania on April 26 2016 with symptoms indicative of a UTI. The isolate was

forwarded to WRNMMC, where susceptibility testing indicated an ESBL phenotype (Table 1).

The isolate was included in the first 6 ESBL-producingE.coliselected for colistin susceptibility

testing, and it was the only isolate to have a MIC of colistin of 4µg/ml (all others had MICs ≤

0.25 µ/ml). Colistin MIC was confirmed by microbroth dilution andmcr1detected by real-time

PCR (6). Whole genome sequencing (WGS) of MRSN 388634 was performed on a PacBio RS II

and Miseq benchtop sequencer.

E. coliMRSN 388634 belonged to ST457, a rareE.coliST first identified in 2008 from a urine

culture in the UK (7). It was subsequently identified from a bloodstream culture in Italy, where it

was found to harbor the carbapenemase genebla KPC-3 andbla CTX-M-55 (8). MRSN 388634 carried

15 antibiotic resistance genes, but no carbapenemases, that were harbored on two plasmids

(Table 2).

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The first plasmid, pMR0516mcr, was 225,707 bp in size and belonged to incompatibility group

F18:A-:B1 (9). BLAST analysis indicated that pMR0516mcr represented a novel IncF plasmid.

Notably, it shares 89 Kb of homologous sequence with pHNSHP45-2, amcr1carrying IncHI2

plasmid described by Liu and colleagues (1). This shared sequence containsmcr1in association

with ISApl1(1), but in pMR0516mcr it is in a different location and orientation (Figure 1).

pMR0516mcr also carried 7 additional antibiotic resistance genes, including the ESBL gene

bla CTX-M-55 (Table 2). The second plasmid, pMR0416ctx, was ~47 Kb in size and was assigned to

IncN (Table 2). It carried 7 antibiotic resistance genes includingbla CTX-M-14 . A complete

description of both plasmids is under preparation.

To the best of our knowledge, this is the first report ofmcr1in the USA. The epidemiology of

MRSN 388634 is noteworthy; the isolate was submitted from a clinic in Pennsylvania, and the

patient reported no travel history within the prior 5 months. To date a further 20 ESBL-

producingE. colifrom patients at the WRNMMC have tested negative formcr1, and are colistin

sensitive. However, as testing has only been ongoing for 3 weeks, it remains unclear what the

true prevalence ofmcr1is in the population. The association betweenmcr1and IncF plasmids

is concerning as these plasmids are vehicles for the dissemination of antibiotic resistance and

virulence genes among theEnterobacteriaceae(9). Continued surveillance to determine the true

frequency for this gene in the USA is critical.

Nucleotide Accession Numbers.TheShort Read Archive (SRA) file for MRSN 388623 has

been deposited at Genbank under Accession number SRP075674.

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Acknowledgements.

This study was funded by the U.S. Army Medical Command, the Global Emerging Infections

Surveillance and Response System,and the Defence Medical Research and Development

Program. All authors declare no conflict of interest.

The identification of specific products or scientific instrumentation does not constitute

endorsement or implied endorsement on the part of the author, DoD, or any component agency.

While we generally excise references to products, companies, manufacturers, organizations, etc.

in government produced works, the abstracts produced and other similarly situated research

presents a special circumstance when such product inclusions become an integral part of the

scientific endeavour.

Material has been reviewed by the Walter Reed Army Institute of Research. There is no

objection to its presentation. The views expressed in this article are those of the author and do

not reflect the official policy of the Department of Army/Navy/Air Force, Department of

Defense, or the U.S. Government.

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Francisco GR, Bueno MF, de Oliveira Garcia D, Knobl T, Moreno AM, Lincopan

Rapoport M, Faccone D, Pasteran F, Ceriana P, Albornoz E, Petroni A, Group

MCR, Corso A.2016.mcr1-mediated colistin resistance in human infections caused by

could contribute to the global spread of themcr1gene. Euro surveillance21.

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Shen J.2016. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in

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1.

Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B,

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Table 1. Antibiotic resistance profile of MRSN 388634

Antibiotic

Amikacin

Amoxacillin/clavulanate

Ampicillin

Aztreonam

Cefazolin

Cefepime

Ceftazidime

Ceftriaxone

Ciprofloxacin

Colistin

Ertapenem

Gentamicin

Imipenem

Levofloxacin

Meropenem

Nitrofurantoin

piperacillin-tazobactam

Tetracycline

Tobramycin

1 MIC (µg/ml)

≤8

16/8

>16

>16

>16

>16

>16

>32

>2

4

≤ 0.25

>8

≤ 0.25

>4

≤ 0.25

≤ 16

4/4

>8

>8

Trimethoprim/sulfamethoxazole >2/38

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1 MIC’s were determined using the BD Phoenix (BD Diagnostics Systems, MD, USA) with

panels NMIC/ID 133 except for colistin, which was performed using E-test and manual

microbroth dilution, and both gave MICs of colistin = 4µg/ml.

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Table 2 Characteristics of plasmids inE.coliMRSN 388634

Name

pMR0516mcr

pMR0416ctx

Size (Kb)

225.7

47

1 Inc

F18:A-:B+

N

2 Copy#

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Antibiotic resistance genes

strA,strB,bla CTX-M-55 ,bla TEM-1B , mcr1,sul2, tet(A), dfrA14

aac(3)IVa , aph(4)Ia , bla CTX-M-14 , fosA3 , mph(A) , floR , sul2

1 Plasmid Incompatibility (Inc) group, as determined by Plasmid Finder version 1.2 (10).

2 Average copy number per cell, normalized to the chromosomal read coverage.

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Figure 1.Comparison of the homologous region containingmcr1shared by pMR0516mcr and

pHNSHP45-2. Open arrows represent coding sequences (Green arrows,mcr1; white arrows,

ISapl1; purple arrows, metabolic function; blue arrows, plasmid replication and maintenance;

grey arrows, hypothetical and unclassified) and indicate direction of transcription. Arrow size is

proportional to the gene length. The grey and blue areas between pMR0516mcr and pHNSHP45-

2 indicate nucleotide identity >99.9% by BLASTN.

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