title: Bacteriophages to reduce gut carriage of antibiotic resistant uropathogens with low impact on microbiota composition.
abstract: 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.
authors.affiliation: Department of Microbiology, Institut Pasteur, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Galtier
authors.affiliation: Department of Microbiology, Institut Pasteur, Paris, France.
authors.forename: Luisa
authors.initials: L
authors.lastname: De Sordi
authors.affiliation: Department of Microbiology, Institut Pasteur, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Maura
authors.affiliation: Institut Pasteur Hub Bioinformatique et Biostatistique - C3BI, USR 3756 IP CNRS - Paris, France.
authors.forename: Harindra
authors.initials: H
authors.lastname: Arachchi
authors.affiliation: Institut Pasteur Hub Bioinformatique et Biostatistique - C3BI, USR 3756 IP CNRS - Paris, France.
authors.forename: Stevenn
authors.initials: S
authors.lastname: Volant
authors.affiliation: Institut Pasteur Hub Bioinformatique et Biostatistique - C3BI, USR 3756 IP CNRS - Paris, France.
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dillies
authors.affiliation: Institut Pasteur Hub Bioinformatique et Biostatistique - C3BI, USR 3756 IP CNRS - Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Debarbieux
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001435:Bacteriophages / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology / Q000821:virology*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology* / Q000821:virology; D005260:Female; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology / Q000821:virology
chemical_list: D000900:Anti-Bacterial Agents