|Isolation and characterization of novel bacteriophages as a potential therapeutic option for Escherichia coli urinary tract infections

Edgar González-Villalobos,Carlos Alberto Eslava-Campos,José Luis Balcázar,Yerisaidy Ortega-García,Gerardo Aparicio-Ozores,Ulises Hernández-Chiñas,José Molina-López,Rosa María Ribas-Aparicio,Gerardo Erbey Rodea Montealegre,Laura Belmont-Monroy

doi:10.1007/s00253-021-11432-6

Abstract

Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC), whose impact can be exacerbated by multidrug-resistant (MDR) strains. Effective control strategies are, therefore, urgently needed. Among them, phage therapy represents a suitable alternative. Here, we describe the isolation and characterization of novel phages from wastewater samples, as well as their lytic activity against biofilm and adherence of UPEC to HEp-2 cells. The results demonstrated that phage vB_EcoM-phiEc1 (ϕEc1) belongs to Myoviridae family, whereas vB_EcoS-phiEc3 (ϕEc3) and vB_EcoS-phiEc4 (ϕEc4) belong to Siphoviridae family. Phages showed lytic activity against UPEC and gut commensal strains. Phage ϕEc1 lysed UPEC serogroups, whereas phages ϕEc3 and ϕEc4 lysed only UTI strains with higher prevalence toward the O25 serogroup. Moreover, phages ϕEc1 and ϕEc3 decreased both biofilm formation and adherence, whereas ϕEc4 was able to decrease adherence but not biofilm formation. In conclusion, these novel phages showed the ability to decrease biofilm and bacterial adherence, making them promising candidates for effective adjuvant treatment against UTIs caused by MDR UPEC strains.Key pointsPhage with lytic activity against MDR UPEC strains were isolated and characterized under in vitro conditions.A novel method was proposed to evaluate phage activity against bacterial adherence in HEp-2 cell..Phages represent a suitable strategy to control infections caused by MDR bacteria.

Highlights

Urinary tract infections (UTIs) are one of the most common health problems, affecting 150 million of people each year worldwide (Tamadonfar et al 2019)
As we live in the antibiotic era, it was easy to assume that these agents would be permanently available in the drug arsenal
Antibiotic resistance is life-threatening, which raises mortality rates, increases human suffering, extends hospitalization periods, and decreases productivity, along with the economic burden that takes a staggering toll in the health care system (Santoro et al 2020; Serra-Burriel et al 2020)

Summary

Introduction

Urinary tract infections (UTIs) are one of the most common health problems, affecting 150 million of people each year worldwide (Tamadonfar et al 2019). In 2007, there were an estimated 10.5 million ambulatory visits for UTI symptoms and 2–3 million emergency department visits in the USA (Foxman 2010, 2014), reaching a cost of more than USD 6 billion on its control and treatment (Mann et al 2017). Community-acquired UTI is the most frequent infection, whose main etiological agent is Escherichia coli. UTIs are usually caused by uropathogenic E. coli (UPEC), with frequencies around 95% for community-acquired and 80% for uncomplicated UTIs in both inpatients and outpatients (Kot 2019). UPEC serogroups O1, O2, O4, O6, O7, O8, O15, O16, O18, O21, O22, O25, 075, and O83 have been associated more frequently with UTIs (Li et al 2010).

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