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Resistance gene transfer: induction of transducing phage by sub-inhibitory concentrations of antimicrobials is not correlated to induction of lytic phage

Stanczak-Mrozek, KI; Laing, KG; Lindsay, JA (2017) Resistance gene transfer: induction of transducing phage by sub-inhibitory concentrations of antimicrobials is not correlated to induction of lytic phage. Journal of Antimicrobial Chemotherapy, 72 (6). pp. 1624-1631. ISSN 1460-2091 https://doi.org/10.1093/jac/dkx056
SGUL Authors: Lindsay, Jodi Anne

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Abstract

Objectives: Horizontal gene transfer of antimicrobial resistance (AMR) genes between clinical isolates via transduction is poorly understood. MRSA are opportunistic pathogens resistant to all classes of antimicrobial agents but currently no strains are fully drug resistant. AMR gene transfer between Staphylococcus aureus isolates is predominantly due to generalized transduction via endogenous bacteriophage, and recent studies have suggested transfer is elevated during host colonization. The aim was to investigate whether exposure to sub-MIC concentrations of antimicrobials triggers bacteriophage induction and/or increased efficiency of AMR gene transfer. Methods: Isolates from MRSA carriers were exposed to nine antimicrobials and supernatants were compared for lytic phage particles and ability to transfer an AMR gene. A new technology, droplet digital PCR, was used to measure the concentration of genes in phage particles. Results: All antibiotics tested induced lytic phage and AMR gene transduction, although the ratio of transducing particles to lytic particles differed substantially for each antibiotic. Mupirocin induced the highest ratio of transducing versus lytic particles. Gentamicin and novobiocin reduced UV-induced AMR transduction. The genes carried in phage particles correlated with AMR transfer or lytic particle activity, suggesting antimicrobials influence which DNA sequences are packaged into phage particles. Conclusions: Sub-inhibitory antibiotics induce AMR gene transfer between clinical MRSA, while combination therapy with an inhibiting antibiotic could potentially alter AMR gene packaging into phage particles, reducing AMR transfer. In a continually evolving environment, pathogens have an advantage if they can transfer DNA while lowering the risk of lytic death.

Item Type: Article
Additional Information: © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Microbiology, 1115 Pharmacology And Pharmaceutical Sciences, 0605 Microbiology, 1108 Medical Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Journal of Antimicrobial Chemotherapy
ISSN: 1460-2091
Dates:
DateEvent
1 February 2017Accepted
20 March 2017Published Online
June 2017Published
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
G0900205Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
URI: https://openaccess.sgul.ac.uk/id/eprint/108709
Publisher's version: https://doi.org/10.1093/jac/dkx056

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