Sex pilus specific bacteriophage to drive bacterial population towards antibiotic sensitivity

Joan Colom,Diego Batista,Siyang Liu,Fernanda Barbosa,Aouatif Belkhiri,Angelo Berchieri,Robert Atterbury,Abiyad Baig,Paul Barrow,Fangzhong Yuan,Marcela Rubio,Lucas Marcelino,Ying Tang

doi:10.1038/s41598-019-48483-9

Joan Colom, Diego Batista + Show 11 more

Open Access

https://doi.org/10.1038/s41598-019-48483-9

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Abstract

Antimicrobial resistance (AMR) is now a major global problem largely resulting from the overuse of antibiotics in humans and livestock. In some AMR bacteria, resistance is encoded by conjugative plasmids expressing sex-pili that can readily spread resistance through bacterial populations. The aim of this study was to use sex pilus-specific (SPS) phage to reduce the carriage of AMR plasmids. Here, we demonstrate that SPS phage can kill AMR Escherichia coli and select for AMR plasmid loss in vitro. For the first time, we also demonstrate that SPS phage can both prevent the spread of AMR Salmonella Enteritidis infection in chickens and shift the bacterial population towards antibiotic sensitivity.

Highlights

Antimicrobial resistance (AMR) results from both regulated and unregulated use of antibiotics and other chemotherapeutic agents for disease treatment in both human and veterinary medicine, and as growth promoters in livestock rearing[1,2]
MS2 was added to a late mid-exponential culture of this strain at a multiplicity of infection (MOI) of 10 and incubated for 24 h
64 ± 12.0% of the bacterial population had lost the plasmid in contrast to a bacterial culture incubated without phage where the loss was 2.5 ± 1.5% (Fig. 1) (P < 0.001)

Summary

Introduction

Antimicrobial resistance (AMR) results from both regulated and unregulated use of antibiotics and other chemotherapeutic agents for disease treatment in both human and veterinary medicine, and as growth promoters in livestock rearing[1,2]. The recent O’Neill report highlighted the role of E. coli, both as a commensal and pathogen, as a significant driver of resistance[4] Much resistance in this organism is plasmid-mediated and transmissible, including resistance to antimicrobials which 20 years ago were chromosomally located such as quinolones and colistin. The World Health Organization (WHO) recently published a list of pathogens prioritised in order of greatest threat to human health and for which new antibiotics are urgently required[15]. This includes carbapenem-resistant and ESBL-producing members of the Enterobacteriaceae, especially E. coli and Klebsiella pneumoniae[15].

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