Bacteriophages to reduce gut carriage of antibiotic resistant uropathogens with low impact on microbiota composition

Abstract

SummaryUropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs) worldwide, causing over 150 million clinical cases annually. There is currently no specific treatment addressing the asymptomatic carriage in the gut of UPEC before they initiate UTIs. This study investigates the efficacy of virulent bacteriophages to decrease carriage of gut pathogens. Three virulent bacteriophages infecting an antibiotic-resistant UPEC strain were isolated and characterized both in vitro and in vivo. A new experimental murine model of gut carriage of E. coli was elaborated and the impact of virulent bacteriophages on colonization levels and microbiota diversity was assessed. A single dose of a cocktail of the three bacteriophages led to a sharp decrease in E. coli levels throughout the gut. We also observed that microbiota diversity was much less affected by bacteriophages than by antibiotics. Therefore, virulent bacteriophages can efficiently target UPEC strains residing in the gut, with potentially profound public health and economic impacts. These results open a new area with the possibility to manipulate specifically the microbiota using virulent bacteriophages, which could have broad applications in many gut-related disorders/diseases and beyond.

The impact of orally administered phages on host immune response and surrounding microbial communities

“…Treatment with a phage cocktail effectively reduced the amount of challenge E. coli in the intestine without significantly affecting the surrounding microbiome at family levels as analyzed by 16S rRNA sequencing. 23 Unlike the extraintestinal E. coli in the aforementioned study, many foodborne pathogens are commensal bacteria in agriculture animals, possibly having an established niche in gut microbiome. In addition, for better application flexibility, phage cocktails designed for agriculture would likely have broad host spectrum.…”

Alternatives to Antibiotics: Phage Lytic Enzymes and Phage Therapy

“…Advantageously, bacteriophages are more specific for certain bacterial strains, such as Clostridium difficile that causes intestinal infections or diarrhea following antibiotic treatment [48]. Also, phage therapy is more sparing than antibiotic-based therapies [49,50]. However, if infection is caused by multiple different bacteria, as is the case with wounds, bacteriophages are far less effective than antibiotics [51].…”

Endolysins of Bacteriophages as an Anti-Methicillin Resistant Staphylococcus aureus Infection in Children: A Narrative Review

“…atopic dermatitis, and infection of the upper respiratory tract in the course of asthma in children (12)(13)(14)(15).…”

“…Oral, subcutaneous or topical phage therapy were often used in children infections for treatment of osteomyelitis, myositis, suppurative wounds, respiratory infections, skin and subcutaneous tissues infections, furunculosis, gastrointestinal infections, and even in septicemia (12,14,73,74).…”