Isolation and genomic characterization of bacteriophages targeting extended-spectrum cephalosporin resistant E. coli

Abstract

Overuse of antibiotics has resulted in the emergence of antibiotic resistant bacteria resulting in bacterial infections in livestock and humans, that can no longer be controlled by these drugs [2]. Third generation cephalosporins are an antibiotic class used in critical situations as the last line of defence, however bacteria have now developed resistance to these drugs [3]. Bacteriophages are viruses which can infect and destroy bacteria, and are being developed as a new therapeutic method for the control and management of bacterial infections in swine. This method offers a highly specific therapy with minimal side effects on the gut microflora [4]. Administration of phages in animal feed has resulted in a reduction of the severity of bacterial infections in addition to a reduction in the shedding of bacteria in faecal matter [2, 5]. This shedding is a major human health concern as it has the potential to transfer antibiotic resistant bacteria and plasmids carrying resistant genes to humans through the faecal to oral route. This project isolated 21 bacteriophages, from three separate sources, that are capable of lysing extended-spectrum cephalosporin (ESC) resistant E. coli. Characterisation of these phages, through electron microscopy and genome sequencing, identified phages belonging to the three different families within the order Caudovirales; Siphoviridae, Myoviridae and Podoviridae. Analysis of the phage genomes resulted in the identification of two clusters within the phages belonging to the Siphoviridae family, named Cluster 1 and 2. Comparison of the specificity of phages sourced from pig farms with (South Australia) and without (Murdoch University) ESC resistant bacteria suggests that highly specific phages can be sourced from locations infected and uninfected by the target bacterial isolate. Three of the phages isolated from Murdoch University have a broad host range of the target ESC resistant E. coli isolates, highlighting these phages for further studies and potential development into therapeutic products

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