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

• Published in: Environmental microbiology 2016-07, Vol.18 (7), p.2237-2245
• Main Authors: Galtier, Matthieu, De Sordi, Luisa, Maura, Damien, Arachchi, Harindra, Volant, Stevenn, Dillies, Marie-Agnès, Debarbieux, Laurent
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteriology; Bacteriophages - genetics; Bacteriophages - physiology; E coli; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - physiology; Escherichia coli - virology; Escherichia coli Infections - drug therapy; Escherichia coli Infections - microbiology; Escherichia coli Infections - virology; Female; Gastrointestinal Microbiome; Gastrointestinal Tract - microbiology; Humans; Life Sciences; Mice; Mice, Inbred BALB C; Microbiology and Parasitology; Urinary Tract Infections - drug therapy; Urinary Tract Infections - microbiology; Urinary Tract Infections - virology
• ISSN: 1462-2912; 1462-2920
• DOI: 10.1111/1462-2920.13284

Summary Uropathogenic 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.