title: Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex.
abstract: Amongst the highly diverse Escherichia coli population, the ST131-O25b:H4 clonal complex is particularly worrisome as it is associated with a high level of antibiotic resistance. The lack of new antibiotics, the worldwide continuous increase of infections caused by MDR bacteria and the need for narrow-spectrum antimicrobial agents have revived interest in phage therapy. In this article, we describe a virulent bacteriophage, LM33_P1, which specifically infects O25b strains, and provide data related to its therapeutic potential.
  
  
  
  A large panel of E. coli strains (n = 283) was used to assess both the specificity and the activity of bacteriophage LM33_P1. Immunology, biochemistry and genetics-based methods confirmed this specificity. Virology methods and sequencing were used to characterize this bacteriophage in vitro, while three relevant mouse models were employed to show its in vivo efficacy.
  
  
  
  Bacteriophage LM33_P1 exclusively infects O25b E. coli strains with a 70% coverage on sequence types associated with high antibiotic resistance (ST131 and ST69). This specificity is due to an interaction with the LPS mediated by an original tail fibre. LM33_P1 also has exceptional intrinsic properties with a high adsorption constant and produces over 300 virions per cell in <10 min. Using animal pneumonia, septicaemia and urinary tract infection models, we showed the in vivo efficacy of LM33_P1 to reduce the bacterial load in several organs.
  
  
  
  Bacteriophage LM33_P1 represents the first weapon that specifically and quickly kills O25b E. coli strains. Therapeutic approaches derived from this bacteriophage could be developed to stop or slow down the spread of the ST131-O25b:H4 drug-resistant clonal complex in humans.
authors.affiliation: AP-HP, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, F-92700 Colombes, France.|INSERM, IAME, UMR 1137, F-75018 Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.|Institut Pasteur, Department of Microbiology, Molecular Biology of Gene in Extremophiles, F-75015 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dufour
authors.affiliation: INSERM, IAME, UMR 1137, F-75018 Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Clermont
authors.affiliation: AP-HP, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, F-92700 Colombes, France.|INSERM, IAME, UMR 1137, F-75018 Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: La Combe
authors.affiliation: AP-HP, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, F-92700 Colombes, France.|INSERM, IAME, UMR 1137, F-75018 Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Messika
authors.affiliation: INSERM, IAME, UMR 1137, F-75018 Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Dion
authors.affiliation: Institut Pasteur, Hub Bioinformatique et Biostatistique - C3BI, USR 3756 IP CNRS, F-75015 Paris, France.
authors.forename: Varun
authors.initials: V
authors.lastname: Khanna
authors.affiliation: INSERM, IAME, UMR 1137, F-75018 Paris, France.|AP-HP, Hôpitaux Universitaires Paris Nord Val-de-Seine, Laboratoire de Génétique Moléculaire, Site Bichat, F-75018 Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
authors.forename: Erick
authors.initials: E
authors.lastname: Denamur
authors.affiliation: AP-HP, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, F-92700 Colombes, France.|INSERM, IAME, UMR 1137, F-75018 Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
authors.forename: Jean-Damien
authors.initials: JD
authors.lastname: Ricard
authors.affiliation: Institut Pasteur, Department of Microbiology, Molecular Biology of Gene in Extremophiles, F-75015 Paris, France laurent.debarbieux@pasteur.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Debarbieux
mesh_terms: D000818:Animals; D003090:Coliphages / Q000254:growth & development* / Q000302:isolation & purification; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000145:classification / Q000235:genetics / Q000502:physiology* / Q000821:virology*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000628:therapy; D016679:Genome, Viral; D005838:Genotype; D051379:Mice; D050296:Microbial Viability; D000071059:Phage Therapy / Q000379:methods; D017422:Sequence Analysis, DNA