Exploring the potential efficacy of phage therapy for biocontrol of foodborne pathogenic extensively drug-resistant Escherichia coli in gastrointestinal tract of rat model

Abstract

AimThe emergence of extensively drug-resistant (XDR) Escherichia coli leaves little or no therapeutic options for the control of these foodborne pathogens. The goal is to isolate, characterize, and assess the potential efficacy of a bacteriophage in the treatment of an induced gastrointestinal tract infection. Main methodsSewage water was used to isolate phage phPE42. Transmission electron microscope was used for the visualization of phage morphology. Lysis profile, growth kinetics, and stability studies were determined. The ability of phage to eradicate biofilms was assessed by crystal violet staining, resazurin assay, compound bright field microscope, and confocal laser scanning microscope (CLSM). Moreover, the efficacy of phage phPE42 as a potential therapy was evaluated in a rat model. Key findingsA newly lytic Myoviridae phage phPE42 was isolated and exhibited broad coverage activity (48.6 %) against E. coli clinical isolates. It demonstrated favorable growth kinetics and relative stability under a variety of challenging conditions. The resazurin colorimetric assay and CLSM provided evidence of phage potential's ability to significantly (P < 0.05) decrease the viability of biofilm-embedded cells. The bacterial burden in animal faeces was effectively eradicated (P < 0.05) by oral administration of phage phPE42. Phage-treated rats exhibited a significant decrease in tissue damage with no signs of inflammation, necrosis, or erosion. Furthermore, phage therapy significantly (P < 0.05) reduced the expression level of the apoptotic marker caspase-3 and the inflammatory cytokine TNF-α. SignificanceTreatment with phage phPE42 is considered a promising alternative therapy for the control of severe foodborne infections spurred by pathogenic XDR E. coli.