In Vitro demonstration of targeted phage therapy and competitive exclusion as a novel strategy for decolonization of Extended-Spectrum-Cephalosporin-Resistant Escherichia coli

Laird, T., Abraham, R., Sahibzada, S.ORCID: 0000-0001-7362-8323, Abraham, S. and O’Dea, M.ORCID: 0000-0002-2757-7585 (2022) In Vitro demonstration of targeted phage therapy and competitive exclusion as a novel strategy for decolonization of Extended-Spectrum-Cephalosporin-Resistant Escherichia coli. Applied and Environmental Microbiology, 88 (7). Art. aem.02276-21.

Abstract

Extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli have disseminated in food-producing animals globally, attributed to horizontal transmission of blaCTX-M variants, as seen in the InCI1-blaCTX-M-1 plasmid. This ease of transmission, coupled with its demonstrated long-term persistence, presents a significant One Health antimicrobial resistance (AMR) risk. Bacteriophage (phage) therapy is a potential strategy in eliminating ESC-R E. coli in food-producing animals; however, it is hindered by the development of phage-resistant bacteria and phage biosafety concerns. Another alternative to antimicrobials is probiotics, with this study demonstrating that AMR-free commensal E. coli, termed competitive exclusion clones (CECs), can be used to competitively exclude ESC-R E. coli. This study isolated and characterized phages that lysed E. coli clones harboring the InCI1-blaCTX-M-1 plasmid, before investigation of the effect and synergy of phage therapy and competitive exclusion as a novel strategy for decolonizing ESC-resistant E. coli. In vitro testing demonstrated superiority in the combined therapy, reducing and possibly eliminating ESC-R E. coli through phage-mediated lysis coupled with simultaneous prevention of regrowth of phage-resistant mutants due to competitive exclusion with the CEC. Further investigation into this combined therapy in vivo is warranted, with on-farm application possibly reducing ESC-R prevalence, while constricting newly emergent ESC-R E. coli outbreaks prior to their dissemination throughout food-producing animals or humans.

Item Type:	Journal Article
Murdoch Affiliation(s):	Antimicrobial Resistance and Infectious Disease Laboratory Harry Butler Institute
Publisher:	American Society for Microbiology
Copyright:	© 2022 American Society for Microbiology
URI:	http://researchrepository.murdoch.edu.au/id/eprint/64601

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