mcr1 – ETIDIoH

A novel #plasmid-mediated #polymyxin #resistance determinant (#mcr-1.8) in #Escherichia coli recovered from broiler #chickens in #Brunei Darussalam (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

A novel plasmid-mediated polymyxin resistance determinant (mcr-1.8) in Escherichia coli recovered from broiler chickens in Brunei Darussalam

Muhd Haziq F Abdul Momin, Apostolos Liakopoulos, David C Bean, Lynette M Phee,David W Wareham

Journal of Antimicrobial Chemotherapy, dkz352, https://doi.org/10.1093/jac/dkz352

Published: 23 August 2019

Issue Section: Research letter

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Sir,

MDR Gram-negative bacteria are identified as critical pathogens and their effective treatment increasingly relies on the polymyxins (polymyxin B, colistin), either alone or as part of unorthodox combination therapies.1 The rapid emergence of polymyxin resistance due to mutations/insertions in genes involved in LPS modifications (lpxCAD, pmrA/B, mgrB, phoP/Q, ccrAB) has been reported among individuals exposed to or treated with polymyxins.1 Of greater concern are increasing reports of resistance due to the acquisition of phosphoethanolamine (PEtN) transferases, enzymes that catalyse the addition of phosphoethanolamine to lipid A, resulting in lower binding affinity of polymyxins.1

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© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

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Keywords: Antibiotics; Drugs Resistance; MCR1; Polymyxins; Poultry; Brunei.

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Activity of #imipenem / #relebactam against #carbapenemase-producing #Enterobacteriaceae with high #colistin resistance (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Activity of imipenem/relebactam against carbapenemase-producing Enterobacteriaceae with high colistin resistance

Jessica Carpenter, Nick Neidig, Alex Campbell, Tanner Thornsberry, Taylor Truex,Tiffany Fortney, Yunliang Zhang, Karen Bush

Journal of Antimicrobial Chemotherapy, dkz354, https://doi.org/10.1093/jac/dkz354

Published: 20 August 2019

Abstract

Objectives

Imipenem/relebactam, an investigational β-lactam/β-lactamase inhibitor combination for treatment of Gram-negative infections, and comparators including ceftazidime/avibactam, piperacillin/tazobactam and colistin were tested for activity against representative carbapenemase-producing Enterobacteriaceae (CPE) isolates.

Methods

MICs of the antimicrobial agents were determined using standard broth microdilution methodology for CPE isolates collected from Indiana patients, primarily during the time frame of 2013–17 (n = 199 of a total of 200 isolates). Inhibitors were tested at 4 mg/L in all combinations.

Results

Of the CPE in the study, 199 produced plasmid-encoded KPC class A carbapenemases; 1 Serratia marcescens isolate produced the SME-1 chromosomal class A carbapenemase. MIC50/MIC90 values of imipenem/relebactam were ≤0.25/0.5 mg/L, whereas MIC50/MIC90 values of ceftazidime/avibactam were 1/2 mg/L. Resistance to colistin was observed in 54% (n = 97) of 180 non-Serratia isolates tested (MIC50 of 4 mg/L). Colistin resistance mechanisms included production of a plasmid-encoded mcr-1-like gene (n = 2) or an inactivated mgrB gene.

Conclusions

Imipenem/relebactam was the most potent agent tested against CPE in this study and may be a useful addition to the antimicrobial armamentarium to treat infections caused by these pathogens.

Issue Section: ORIGINAL RESEARCH

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Colistin; MCR1; Enterobacteriaceae; Imipenem; Relebactam.

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#Polymyxin #resistance in #Klebsiella pneumoniae: multifaceted mechanisms utilized in the presence and absence of the #plasmid-encoded phosphoethanolamine transferase gene #mcr-1 (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Polymyxin resistance in Klebsiella pneumoniae: multifaceted mechanisms utilized in the presence and absence of the plasmid-encoded phosphoethanolamine transferase gene mcr-1

Sue C Nang, Mei-Ling Han, Heidi H Yu, Jiping Wang, Von Vergel L Torres, Chongshan Dai,Tony Velkov, Marina Harper, Jian Li

Journal of Antimicrobial Chemotherapy, dkz314, https://doi.org/10.1093/jac/dkz314

Published: 31 July 2019

Abstract

Objectives

Until plasmid-mediated mcr-1 was discovered, it was believed that polymyxin resistance in Gram-negative bacteria was mainly mediated by the chromosomally-encoded EptA and ArnT, which modify lipid A with phosphoethanolamine (pEtN) and 4-amino-4-deoxy-L-arabinose (L-Ara4N), respectively. This study aimed to construct a markerless mcr-1 deletion mutant in Klebsiella pneumoniae, validate a reliable reference gene for reverse transcription quantitative PCR (RT–qPCR) and investigate the interactions among mcr-1, arnT and eptA, in response to polymyxin treatments using pharmacokinetics/pharmacodynamics (PK/PD).

Methods

An isogenic markerless mcr-1 deletion mutant (II-503Δmcr-1) was generated from a clinical K. pneumoniae II-503 isolate. The efficacy of different polymyxin B dosage regimens was examined using an in vitro one-compartment PK/PD model and polymyxin resistance was assessed using population analysis profiles. The expression of mcr-1, eptA and arnT was examined using RT–qPCR with a reference gene pepQ, and lipid A was profiled using LC-MS. In vivo polymyxin B efficacy was investigated in a mouse thigh infection model.

Results

In K. pneumoniae II-503, mcr-1 was constitutively expressed, irrespective of polymyxin exposure. Against II-503Δmcr-1, an initial bactericidal effect was observed within 4 h with polymyxin B at average steady-state concentrations of 1 and 3 mg/L, mimicking patient PK. However, substantial regrowth and concomitantly increased expression of eptA and arnT were detected. Predominant L-Ara4N-modified lipid A species were detected in II-503Δmcr-1 following polymyxin B treatment.

Conclusions

This is the first study demonstrating a unique markerless deletion of mcr-1 in a clinical polymyxin-resistant K. pneumoniae. The current polymyxin B dosage regimens are suboptimal against K. pneumoniae, regardless of mcr, and can lead to the emergence of resistance.

Issue Section: ORIGINAL RESEARCH

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Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; MCR1; Plasmids; Polymyxin B.

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Emergence of a hybrid #plasmid derived from IncN1-F33:A−:B− and #mcr-1-bearing plasmids mediated by IS26 (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Emergence of a hybrid plasmid derived from IncN1-F33:A−:B− and mcr-1-bearing plasmids mediated by IS26

Dandan He, Yingying Zhu, Ruichao Li, Yushan Pan, Jianhua Liu, Li Yuan,Gongzheng Hu

Journal of Antimicrobial Chemotherapy, dkz327, https://doi.org/10.1093/jac/dkz327

Published: 30 July 2019

Abstract

Objectives

To characterize the complete sequences of four plasmids in MCR-1-producing clinical Escherichia coli strain D72, and to depict the formation mechanism and characteristics of the cointegrate plasmid derived from the pD72-mcr1 and pD72-F33 plasmids.

Methods

The genetic profiles of plasmids in strain D72 and its transconjugant were determined by conjugation, S1-PFGE, Southern hybridization, WGS analysis and PCR. Plasmid sequences were analysed with bioinformatic tools. The traits of the fusion plasmid were characterized by cointegration, stability and conjugation assays.

Results

Strain D72, belonging to ST1114, contained four plasmids, including mcr-1-carrying pD72-mcr1, blaCTX-M-55-carrying pD72-F33, blaTEM-238-bearing pD72-IncP and pD72-IncX1 carrying aph(3′)-Ia, qnrS2 and floR. A single plasmid, pD72C, in the transconjugant was found to be larger than any plasmid in the original strain D72. Sequence analysis showed that pD72C was the fusion product of pD72-mcr1 and pD72-F33, and the recombinant event involved an intermolecular replicative mechanism. Plasmid fusion occurred at a frequency of 1.75 × 10−4 cointegrates per transconjugant. The fusion plasmid presented a high stability and conjugation frequency of 8.00 × 10−3.

Conclusions

To our knowledge, this is the first report of the IS26-mediated fusion of an IncN1-F33:A−:B− plasmid and an mcr-1-carrying phage-like plasmid, providing evidence for the important role of IS26 in the recombination of plasmids. The biological advantages of the fusion plasmid indicated that the fusion event presumably plays a potential role in the dissemination of mcr-1.

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Keywords: Antibiotics; Drugs Resistance; Colistin; E. Coli; MCR1; Plasmids.

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Polyclonal #gut #colonization with extended-spectrum #cephalosporin- and/or #colistin-resistant #Enterobacteriaceae: a normal status for #hotel employees on the island of #Zanzibar, Tanzania (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Polyclonal gut colonization with extended-spectrum cephalosporin- and/or colistin-resistant Enterobacteriaceae: a normal status for hotel employees on the island of Zanzibar, Tanzania

Thomas Büdel, Esther Kuenzli, Mathieu Clément, Odette J Bernasconi, Jan Fehr,Ali Haji Mohammed, Nadir Khatib Hassan, Jakob Zinsstag, Christoph Hatz,Andrea Endimiani

Journal of Antimicrobial Chemotherapy, dkz296, https://doi.org/10.1093/jac/dkz296

Published: 30 July 2019

Abstract

Objectives

For low-income countries, data regarding the intestinal colonization with extended-spectrum cephalosporin-resistant (ESC-R) and colistin-resistant (CST-R) Enterobacteriaceae in the community are still scarce. Here, we investigated this phenomenon by analysing hotel employees in Zanzibar.

Methods

During June to July 2018, rectal swabs from 59 volunteers were screened implementing selective enrichments and agar plates. Species identification was achieved using MALDI-TOF MS. Strains were characterized using microdilution panels (MICs), microarray, PCRs for mcr-1/-8, repetitive extragenic palindromic-PCR (rep-PCR) and WGS.

Results

Colonization prevalence with ESC-R-, CST-R- and mcr-1-positive Enterobacteriaceae were 91.5%, 66.1% and 18.6%, respectively (average: 2.2 strains per volunteer). Overall, 55 ESC-R Escherichia coli (3 also CST-R), 33 ESC-R Klebsiella pneumoniae (1 also CST-R), 17 CST-R E. coli and 21 CST-R K. pneumoniae were collected. The following main resistance genes were found: ESC-R E. coli (blaCTX-M-15-like, 51.0%), ESC-R K. pneumoniae (blaCTX-M-9-like, 42.9%), CST-R E. coli (mcr-1, 55%) and CST-R K. pneumoniae (D150G substitution in PhoQ). ESBL-producing E. coli mainly belonged to ST361, ST636 and ST131, whereas all those that were mcr-1 positive belonged to ST46 that carried mcr-1 in a 33 kb IncX4 plasmid. ESBL-producing K. pneumoniae mainly belonged to ST17, ST1741 and ST101, whereas CST-R strains belonged to ST11.

Conclusions

We recorded remarkably high colonization prevalence with ESC-R and/or CST-R Enterobacteriaceae in hotel staff. Further research in the local environment, livestock and food chain is warranted to understand this phenomenon. Moreover, as Zanzibar is a frequent holiday destination, attention should be paid to the risk of international travellers becoming colonized and thereby importing life-threatening pathogens into their low-prevalence countries.

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Keywords: Enterobacteriaceae; Antibiotics; Drugs Resistance; Cephalosporins; Colistin; MCR1; Tanzania.

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Co-occurrence of #mcr1 and #mcr3 #genes in a single #Escherichia coli in #NZ (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Co-occurrence of mcr-1 and mcr-3 genes in a single Escherichia coli in New Zealand

Julie Creighton, Trevor Anderson, Julia Howard, Kristin Dyet, Xiaoyun Ren,Joshua Freeman

Journal of Antimicrobial Chemotherapy, dkz311, https://doi.org/10.1093/jac/dkz311

Published: 24 July 2019

Issue Section: Research letter

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Sir,

The discovery of the plasmid-mediated colistin resistance gene mcr-1, first identified in 2015 among both clinical and animal isolates in China, raised concerns about pan-resistant bacteria.1 A plethora of publications quickly followed, suggesting mcr-1 was already established in many countries and across many continents, in various bacterial species, on a variety of plasmids types, and in bacteria isolated from diverse animal species, environmental sources and human health settings.2 Furthermore, several other mcr-like genes and gene variants have since been discovered.2,3

Colistin is among a diminishing group of antimicrobial agents available for…

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Keywords: Antibiotics; Drugs Resistance; Colistin; E. Coli; New Zealand.

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#Plasmid-Mediated #mcr-1 #Colistin #Resistance in #Escherichia coli from a Black Kite in #Russia (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Plasmid-Mediated mcr-1 Colistin Resistance in Escherichia coli from a Black Kite in Russia

Hassan Tarabai, Adam Valcek, Ivana Jamborova, Sergey V. Vazhov, Igor V. Karyakin, Rainer Raab, Ivan Literak, Monika Dolejska

DOI: 10.1128/AAC.01266-19

ABSTRACT

The gene mcr-1 conferring resistance to last-line antibiotic colistin has been reported globally. Here we describe the first detection of plasmid-mediated colistin resistance in Russian wildlife, an isolate of Escherichia coli sequence type 2280 from a black kite (Milvus migrans), scavenging raptor. Whole genome sequencing and plasmid transferability experiments revealed that mcr-1.1 was located on a conjugative IncI2 plasmid pDR164 (59891 bp). Migratory Black Kites may contribute to the global spread of mobile colistin resistance.

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Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; E. Coli; Wild Birds; Russia.

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