Conjugal Transfer, #WGS, and #Plasmid Analysis of Four #mcr1–bearing Isolates from #US Patients (Antimicrob Agents Chemother., asbtract)

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

Conjugal Transfer, Whole Genome Sequencing, and Plasmid Analysis of Four mcr-1–bearing Isolates from U.S. Patients

Wenming Zhu, Adrian Lawsin, Rebecca L. Lindsey, Dhwani Batra, Kristen Knipe, Brian B. Yoo, K. Allison Perry, Lori A. Rowe, David Lonsway, Maroya S. Waters, J. Kamile Rasheed, Alison Laufer Halpin

DOI: 10.1128/AAC.02417-18

 

ABSTRACT

Four Enterobacteriaceae clinical isolates bearing mcr-1 gene-harboring plasmids were characterized. All isolates demonstrated the ability to transfer colistin resistance to E. coli;plasmids were stable in conjugants after multiple passages on non–selective media. mcr-1 was located on an IncX4 (n=3) or IncN (n=1) plasmid. The IncN plasmid harbored 13 additional antimicrobial resistance genes. Results indicate the mcr-1-bearing plasmids in this study are highly transferable in vitro and stable in the recipients.

This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Keywords: Antibiotics; Drugs Resistance; USA; E. Coli; Enterobacteriaceae; Colistin; MCR1.

—–

Advertisements

Updated #Prevalence of #mcr-like Genes among #Escherichia coli and #Klebsiella pneumoniae in SENTRY Program and Characterization of mcr-1.11 Variant (Antimicrob Agents Chemother., abstract)

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

Updated Prevalence of mcr-like Genes among Escherichia coli and Klebsiella pneumoniae in SENTRY Program and Characterization of mcr-1.11 Variant

Lalitagauri M. Deshpande, Cory Hubler, Andrew P. Davis, Mariana Castanheira

DOI: 10.1128/AAC.02450-18

 

ABSTRACT

Increased prevalence of infections caused by Gram-negative pathogens that are multidrug resistant has prompted the reconsideration of polymyxins as therapeutic options.…

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Polymyxins; MCR1.

——

Detection of #mcr-mediated #colistin #resistance in #Escherichia coli isolated from #pigs in small-scale #farms in #Cambodia (Antimicrob Agents Chemother., abstract)

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

Detection of mcr-mediated colistin resistance in Escherichia coli isolated from pigs in small-scale farms in Cambodia

G Ström Hallenberg, S Börjesson, S Sokerya, T Sothyra, U Magnusson

DOI: 10.1128/AAC.02241-18

 

ABSTRACT

Colistin is today considered a last-line antimicrobial for the treatment of infections in humans caused by multidrug-resistant Enterobacteriaceae [1]. The dissemination of colistin resistance has received increased attention since a mobilized gene conferring resistance to colistin, mcr-1, was described in Enterobacteriaceae from humans and food-producing animals in China in 2015 [2], and additional gene homologs have since been identified [3-15].

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; Pigs; Cambodia.

—–

#Salmonella harbouring the #mcr1 gene isolated from #food in #China between 2012 and 2016 (J Antimicrob Chemother., abstract)

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

Salmonella harbouring the mcr-1 gene isolated from food in China between 2012 and 2016

Yujie Hu, Séamus Fanning, Xin Gan, Chang Liu, Scott Nguyen, Meimei Wang, Wei Wang, Tao Jiang, Jin Xu, Fengqin Li

Journal of Antimicrobial Chemotherapy, dky496, https://doi.org/10.1093/jac/dky496

Published: 02 January 2019

___

Sir,

In November 2015, plasmid-mediated transferable colistin resistance encoded by the mcr-1 gene in Escherichia coli and Klebsiella pneumonia isolates was reported in China with a high rate of in vitro horizontal transfer (10−1–10−3 cells per recipient cell by conjugation).1 At that time, the mcr-1 gene had already been identified in >30 countries across five continents, with novel mcr-2mcr-3mcr-4 and mcr-5 genes being reported subsequently.2–5 Recently, a surveillance study was performed on mainland China to investigate the prevalence of the mcr-1 gene in foodborne Salmonella isolates isolated from various food matrices and others collected…

Issue Section:  Research letter

© 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)

Keywords: Food Safety; Antibiotics; Drugs Resistance; MCR1; Colistin; Salmonella spp.

—–

#Fitness cost of a #mcr-1-carrying IncHI2 #plasmid (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Fitness cost of a mcr-1-carrying IncHI2 plasmid

Ke Ma, Yu Feng, Zhiyong Zong

Published: December 26, 2018 / DOI: https://doi.org/10.1371/journal.pone.0209706

 

Abstract

IncHI2 is a common type of large mcr-1-carrying plasmids that have been found worldwide. Large plasmids could impose metabolic burden for host bacterial strains, we therefore examine the stability and fitness cost of a mcr-1-carrying 265.5-kb IncHI2 plasmid, pMCR1_1943, in Escherichia coli in nutrient-rich LB and nutrient-restricted M9 broth. Stability tests revealed that pMCR1_1943 was stably maintained with a stability frequency of 0.99±0.01 (mean ± standard deviation) after 880 generations in LB and 0.97±0.00 after 220 generations in M9 broth. Relative fitness (expressed as w, defined as relative fitness of the plasmid-carrying strain compared to the plasmid-free progenitor strain) was examined using the 24-h head to head competitions. pMCR1_1943 initially imposed costs (w, 0.88±0.03 in LB, 0.87±0.01 in M9) but such costs were largely reduced after 14-day cultures (w, 0.97±0.03 in LB, 0.95±0.03 in M9). The stable maintenance and the largely compensated cost after passage may contribute to the wide spread of mcr-1-carrying IncHI2 plasmids. To investigate potential mechanisms for the reduced fitness cost, we performed whole genome sequencing and single nucleotide polymorphism calling for the competitor strains. We identified that molecular chaperone-encoding dnaK, cell division protein-encoding cpoB and repeat protein-encoding rhsC were associated with the cost reduction for pMCR1_1943, which may represent new mechanisms for host bacterial strains to compensate fitness costs imposed by large plasmids and warrant further studies.

___

Citation: Ma K, Feng Y, Zong Z (2018) Fitness cost of a mcr-1-carrying IncHI2 plasmid. PLoS ONE 13(12): e0209706. https://doi.org/10.1371/journal.pone.0209706

Editor: Günther Koraimann, University of Graz, AUSTRIA

Received: September 20, 2018; Accepted: December 10, 2018; Published: December 26, 2018

Copyright: © 2018 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Short reads of genome sequences of the strains in the present study have been deposited into Sequence Read Archive of GenBank under the accession no. SRR7031288, SRR7031297, SRR7031306, SRR7031313, SRR7031315, SRR7031316, SRR7031320, SRR7031295.

Funding: ZZ was supported by grants from the National Natural Science Foundation of China (project no. 81772233 and 81661130159) and the Newton Advanced Fellowship, Royal Society, UK (NA150363). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1.

——

#Azidothymidine [#AZT] produces synergistic #activity in combination with #colistin against #antibiotic-resistant #Enterobacteriaceae (Antimicrob Agents Chemother., abstract)

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

Azidothymidine produces synergistic activity in combination with colistin against antibiotic-resistant Enterobacteriaceae

Yanmin Hu, Yingjun Liu, Anthony Coates

DOI: 10.1128/AAC.01630-18

 

ABSTRACT

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, antibiotic-resistant Enterobacteriaceae is prevalent and extremely difficult to treat. Reusing existing drugs and rejuvenating the therapeutic potential of existing antibiotics represent an attractive novel strategy. Azidothymidine (AZT) is an antiretroviral drug which is used in combination with other antivirals to prevent and to treat HIV/AIDS. AZT is also active against Gram-negative bacteria but has not been developed for that purpose. Here we investigated in vitro and in vivo efficacy of AZT in combination with colistin against antibiotic-resistant Enterobacteriaceae including extended-spectrum beta-lactamase (ESBL), New Delhi metallo-beta-lactamase 1 (NDM) or the mobilized colistin resistance (mcr-1) producing strains. Minimum inhibitory concentration was determined using the broth microdilution method. The combinatory effect of AZT and colistin was examined using the checkerboard method and time-kill analysis. A murine peritoneal infection model was used to test the therapeutic effect of the combination of AZT and colistin. Fractional inhibitory concentration index from checkerboard assay demonstrated that AZT synergized with colistin against 61% and 87% of ESBL-producing Escherichia coli and Klebsiella pneumoniae, respectively, 100% of NDM-1-producing strains and 92% of mcr-1 producing E. coli. Time-kill analysis demonstrated significant synergistic activities when AZT was combined with colistin. In the murine peritoneal infection model, AZT in combination with colistin showed augmented activities of both drugs in the treatment of NDM-1 K. pneumoniae and mcr-1 E. coli infections. AZT and colistin combination poses a potential to be used coherently to treat antibiotic-resistant Enterobacteriaceae infections.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antivirals; Antibiotics; Drugs Resistance; Colistin; AZT; MCR1; Enterobacteriaceae.

——

Novel partners with #colistin to increase its in vivo therapeutic effectiveness and prevent the occurrence of colistin #resistance in #NDM- and #MCR-co-producing #Ecoli in a murine infection model (J Antimicrob Chemother., abstract)

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

Novel partners with colistin to increase its in vivotherapeutic effectiveness and prevent the occurrence of colistin resistance in NDM- and MCR-co-producing Escherichia coli in a murine infection model

Yang Yu, Timothy R Walsh, Run-Shi Yang, Mei Zheng, Meng-Chao Wei, Jonathan M Tyrrell, Yang Wang, Xiao-Ping Liao, Jian Sun, Ya-Hong Liu

Journal of Antimicrobial Chemotherapy, dky413, https://doi.org/10.1093/jac/dky413

Published: 20 October 2018

 

Abstract

Objectives

The emergence of NDM- and MCR-1-co-producing Escherichia coli has compromised the use of carbapenems and colistin, which are critically important in clinical therapy, and represents a severe threat to public health worldwide. Here, we demonstrate synergism of colistin combined with existing antibiotics as a potential strategy to overcome XDR E. coli co-harbouring NDM and MCR-1 genes.

Methods

To comprehensively evaluate their combined activity, antibiotic combinations were tested against 34 different E. coli strains carrying both NDM and MCR-1 genes. Antibiotic resistance profiles and molecular characteristics were investigated by susceptibility testing, PCR, MLST, S1-PFGE and WGS. Antibiotic synergistic efficacy was evaluated through in vitro chequerboard experiments and dose–response assays. A mouse model was used to confirm active combination therapies. Additionally, combinations were tested for their ability to prevent high-level colistin-resistant mutants (HLCRMs).

Results

Combinations of colistin with rifampicin, rifabutin and minocycline showed synergistic activity against 34 XDR NDM- and MCR-1-co-producing E. coli strains, restoring, in part, susceptibility to both colistin and the partnering antibiotics. The therapeutic effectiveness of colistin combined with rifampicin or minocycline was demonstrated in a mouse model. Furthermore, colistin plus rifampicin showed significant activity in preventing the occurrence of HLCRMs.

Conclusions

The synergism of colistin in combinations with rifampicin, rifabutin or minocycline offers viable therapeutic alternatives against XDR NDM- and MCR-positive E. coli.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2018. 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)

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Colistin; E. Coli; Rifampicin; Rifabutin; Minocycline; MCR; NDM.

——