#Evolution of a 72-kb cointegrant, conjugative #multiresistance #plasmid from early CA #MRSA isolates (Antimicrob Agents Chemother., abstract)

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

Evolution of a 72-kb cointegrant, conjugative multiresistance plasmid from early community-associated methicillin-resistant Staphylococcus aureus isolates

Karina Yui Eto, Neville Firth, Amy M. Davis, Stephen M. Kwong, Marcelina Krysiak, Yung Thin Lee, Frances G. O’Brien, Warren B. Grubb, Geoffrey W. Coombs, Charles S. Bond, Joshua P. Ramsay

DOI: 10.1128/AAC.01560-19

 

ABSTRACT

Horizontal transfer of plasmids encoding antimicrobial-resistance and virulence determinants has been instrumental in Staphylococcus aureus evolution, including the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA). In the early 1990s the first CA-MRSA isolated in Western Australia (WA), WA-5, encoded cadmium, tetracycline and penicillin-resistance genes on plasmid pWBG753 (∼30 kb). WA-5 and pWBG753 appeared only briefly in WA, however, fusidic-acid-resistance plasmids related to pWBG753 were also present in the first European CA-MRSA at the time. Here we characterized a 72-kb conjugative plasmid pWBG731 present in multiresistant WA-5-like clones from the same period. pWBG731 was a cointegrant formed from pWBG753 and a pWBG749-family conjugative plasmid. pWBG731 carried mupirocin, trimethoprim, cadmium and penicillin-resistance genes. The stepwise evolution of pWBG731 likely occurred through the combined actions of IS257, IS257-dependent miniature inverted-repeat transposable elements (MITEs) and the BinL resolution system of the β-lactamase transposon Tn552. An evolutionary intermediate ∼42-kb non-conjugative plasmid pWBG715, possessed the same resistance genes as pWBG731 but retained an integrated copy of the small tetracycline-resistance plasmid pT181. IS257 likely facilitated replacement of pT181 with conjugation genes on pWBG731, thus enabling autonomous transfer. Like conjugative plasmid pWBG749, pWBG731 also mobilized non-conjugative plasmids carrying oriT mimics. It seems likely that pWBG731 represents the product of multiple recombination events between the WA-5 pWBG753 plasmid and other mobile genetic elements present in indigenous CA-MSSA. The molecular evolution of pWBG731 saliently illustrates how diverse mobile genetic elements can together facilitate rapid accrual and horizontal dissemination of multiresistance in S. aureus CA-MRSA.

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

Keywords: Antibiotics; Drugs Resistance; MRSA; Staphylococcus aureus; Plasmids.

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#Plasmid-mediated #quinolone #resistance: Mechanisms, detection, and #epidemiology in the #Arab countries (Infect Genet Evol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Infect Genet Evol. 2019 Sep 4:104020. doi: 10.1016/j.meegid.2019.104020. [Epub ahead of print]

Plasmid-mediated quinolone resistance: Mechanisms, detection, and epidemiology in the Arab countries.

Yassine I1, Rafei R2, Osman M2, Mallat H2, Dabboussi F2, Hamze M1.

Author information: 1 Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon. Electronic address: mhamze@monzerhamze.com. 2 Laboratoire Microbiologie Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon.

 

Abstract

Quinolones are an important antimicrobial class used widely in the treatment of enterobacterial infections. Although there are multiple mechanisms of quinolone resistance, attention should be paid to plasmid-mediated genes due to their ability to facilitate the spread of quinolone resistance, the selection of mutants with a higher-level of quinolone resistance, and the promotion of treatment failure. Since their discovery in 1998, plasmid-mediated quinolone resistance (PMQR) mechanisms have been reported more frequently worldwide especially with the extensive use of quinolones in humans and animals. Nevertheless, data from the Arab countries are rare and often scattered. Understanding the prevalence and distribution of PMQR is essential to stop the irrational use of quinolone in these countries. This manuscript describes the quinolone resistance mechanisms and particularly PMQR among Enterobacteriaceae as well as their methods of detection. Then the available data on the epidemiology of PMQR in clinical and environmental isolates from the Arab countries are extensively reviewed along with the other associated resistance genes. These data shows a wide dissemination of PMQR genes among Enterobacteriaceae isolates from humans, animals, and environments in these countries with increasing rates over the years and a common association with other antibiotic resistance genes as blaCTX-M-15. The incontrovertible emergence of PMQR in the Arab countries highlights the pressing need for effective stewardship efforts to prevent the selection of a higher rate of quinolone resistance and to preserve these crucial antibiotics.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS: Arab countries; Detection; Epidemiology; Molecular mechanisms; Plasmid-mediated quinolone resistance (PMQR); Quinolones

PMID: 31493557 DOI: 10.1016/j.meegid.2019.104020

Keywords: Antibiotics; Drugs Resistance; Quinolones; Enterobacteriaceae.

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Complete Nucleotide #Sequence of a Novel #Plasmid Bearing the High-Level #Tigecycline #Resistance Gene, tet(X4) (Antimicrob Agents Chemother., abstract)

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

Complete Nucleotide Sequence of a Novel Plasmid Bearing the High-Level Tigecycline Resistance Gene, tet(X4)

Liang-Xing Fang, Chong Chen, Dong-Ling Yu, Ruan-Yang Sun, Chao-Yue Cui, Liang Chen, Xiao-Ping Liao, Ya-Hong Liu, Jian Sun

DOI: 10.1128/AAC.01373-19

 

ABSTRACT

We reported the complete nucleotide sequence of a tet(X4)-carrying plasmid, pSTB20-1T, from a tigecycline-resistant Escherichia coli isolate in China. Sequence analysis indicated that pSTB20-1T contains a hybrid plasmid backbone and a tet(X4)-containing multidrug resistance region, likely originated through recombination of multiple plasmids. tet(X4) was flanked by two ISCR2, which may be responsible for tet(X4) mobilization. The occurrence and transmission of this novel hybrid plasmid may exacerbate the spread of the clinically significant tet(X4) gene.

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

Keywords: Antibiotics; Drugs Resistance; E. Coli; Tigecycline; China.

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Conjugative IncX 1 #plasmid harboring #colistin #resistance gene #mcr-5.1 in #E coli isolated from #chicken rice retailed in #Singapore (Antimicrob Agents Chemother., abstract)

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

Conjugative IncX 1 plasmid harboring colistin resistance gene mcr-5.1 in E. coli isolated from chicken rice retailed in Singapore

Siyao Guo, Moon Y.F. Tay, Aung Kyaw Thu, Kelyn Lee Ghee Seow, Yang Zhong, Lee Ching Ng, Joergen Schlundt

DOI: 10.1128/AAC.01043-19

 

ABSTRACT

Colistin is regarded as one of the last resort antimicrobials to Gram-negative bacterial infection (1).…

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

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR5; Plasmids; Food Safety; Singapore.

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#Evolution of #Outbreak-Causing #Carbapenem-Resistant #Klebsiella pneumoniae ST258 at a Tertiary Care #Hospital over 8 Years (mBio, abstract)

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

Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years

Jane W. Marsh, Mustapha M. Mustapha, Marissa P. Griffith, Daniel R. Evans, Chinelo Ezeonwuka, A. William Pasculle, Kathleen A. Shutt, Alexander Sundermann, Ashley M. Ayres,Ryan K. Shields, Ahmed Babiker, Vaughn S. Cooper, Daria Van Tyne, Lee H. Harrison

Robert A. Bonomo, Editor

DOI: 10.1128/mBio.01945-19

 

ABSTRACT

Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains belonging to sequence type 258 (ST258) are frequent causes of hospital-associated outbreaks and are a major contributor to the spread of carbapenemases. This genetic lineage emerged several decades ago and remains a major global health care challenge. In this study, genomic epidemiology was used to investigate the emergence, evolution, and persistence of ST258 carbapenem-resistant K. pneumoniae outbreak-causing lineages at a large tertiary care hospital over 8 years. A time-based phylogenetic analysis of 136 ST258 isolates demonstrated the succession of multiple genetically distinct ST258 sublineages over the 8-year period. Ongoing genomic surveillance identified the emergence and persistence of several distinct clonal ST258 populations. Patterns of multidrug resistance determinants and plasmid replicons were consistent with continued evolution and persistence of these populations. Five ST258 outbreaks were documented, including three that were caused by the same clonal lineage. Mutations in genes encoding effectors of biofilm production and iron acquisition were identified among persistent clones. Two emergent lineages bearing K. pneumoniae integrative conjugative element 10 (ICEKp10) and harboring yersiniabactin and colibactin virulence factors were identified. The results show how distinct ST258 subpopulations have evolved and persisted within the same hospital over nearly a decade.

 

IMPORTANCE

The carbapenem class of antibiotics is invaluable for the treatment of selected multidrug-resistant Gram-negative pathogens. The continued transmission of carbapenem-resistant bacteria such as ST258 K. pneumoniae is of serious global public health concern, as treatment options for these infections are limited. This genomic epidemiologic investigation traced the natural history of ST258 K. pneumoniae in a single health care setting over nearly a decade. We found that distinct ST258 subpopulations have caused both device-associated and ward-associated outbreaks, and some of these populations remain endemic within our hospital to the present day. The finding of virulence determinants among emergent ST258 clones supports the idea of convergent evolution of drug-resistant and virulent CRKP strains and highlights the need for continued surveillance, prevention, and control efforts to address emergent and evolving ST258 populations in the health care setting.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Klebsiella pneumoniae; Nosocomial outbreaks.

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#Genomic #investigation of #Staphylococcus aureus recovered from #Gambian #women and #newborns following an oral dose of intra-partum #azithromycin (J Antimicrob Chemother., abstract)

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

Genomic investigation of Staphylococcus aureus recovered from Gambian women and newborns following an oral dose of intra-partum azithromycin

Abdoulie Bojang, Sarah L Baines, Liam Donovan, Romain Guerillot, Kerrie Stevens,Charlie Higgs, Christian Bottomley, Ousman Secka, Mark B Schultz,Anders Gonçalves da Silva, Torsten Seemann, Timothy P Stinear, Anna Roca,Benjamin P Howden

Journal of Antimicrobial Chemotherapy, dkz341, https://doi.org/10.1093/jac/dkz341

Published: 19 August 2019

 

Abstract

Background

Oral azithromycin given during labour reduces carriage of bacteria responsible for neonatal sepsis, including Staphylococcus aureus. However, there is concern that this may promote drug resistance.

Objectives

Here, we combine genomic and epidemiological data on S. aureus isolated from mothers and babies in a randomized intra-partum azithromycin trial (PregnAnZI) to describe bacterial population dynamics and resistance mechanisms.

Methods

Participants from both arms of the trial, who carried S. aureus in day 3 and day 28 samples post-intervention, were included. Sixty-six S. aureus isolates (from 7 mothers and 10 babies) underwent comparative genome analyses and the data were then combined with epidemiological data. Trial registration (main trial): ClinicalTrials.gov Identifier NCT01800942.

Results

Seven S. aureus STs were identified, with ST5 dominant (n = 40, 61.0%), followed by ST15 (n = 11, 17.0%). ST5 predominated in the placebo arm (73.0% versus 49.0%, P = 0.039) and ST15 in the azithromycin arm (27.0% versus 6.0%, P = 0.022). In azithromycin-resistant isolates, msr(A) was the main macrolide resistance gene (n = 36, 80%). Ten study participants, from both trial arms, acquired azithromycin-resistant S. aureus after initially harbouring a susceptible isolate. In nine (90%) of these cases, the acquired clone was an msr(A)-containing ST5 S. aureus. Long-read sequencing demonstrated that in ST5, msr(A) was found on an MDR plasmid.

Conclusions

Our data reveal in this Gambian population the presence of a dominant clone of S. aureus harbouring plasmid-encoded azithromycin resistance, which was acquired by participants in both arms of the study. Understanding these resistance dynamics is crucial to defining the public health drug resistance impacts of azithromycin prophylaxis given during labour in Africa.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Macrolides; Azithromycin; Pregnancy; Gambia.

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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

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

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