Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex

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 narr...

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Published in:Journal of antimicrobial chemotherapy 2016-11, Vol.71 (11), p.3072-3080
Main Authors: Dufour, Nicolas, Clermont, Olivier, La Combe, Béatrice, Messika, Jonathan, Dion, Sara, Khanna, Varun, Denamur, Erick, Ricard, Jean-Damien, Debarbieux, Laurent
Format: Article
Language:English
Subjects:
Animals
Bacteriology
Coliphages - growth & development
Coliphages - isolation & purification
Disease Models, Animal
Escherichia coli - classification
Escherichia coli - genetics
Escherichia coli - physiology
Escherichia coli - virology
Escherichia coli Infections - microbiology
Escherichia coli Infections - therapy
Genome, Viral
Genotype
Life Sciences
Mice
Microbial Viability
Microbiology and Parasitology
Phage Therapy - methods
Sequence Analysis, DNA
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description 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
doi_str_mv 10.1093/jac/dkw253
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LM33_P1 also has exceptional intrinsic properties with a high adsorption constant and produces over 300 virions per cell in &lt;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. 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subjects Animals
Bacteriology
Coliphages - growth & development
Coliphages - isolation & purification
Disease Models, Animal
Escherichia coli - classification
Escherichia coli - genetics
Escherichia coli - physiology
Escherichia coli - virology
Escherichia coli Infections - microbiology
Escherichia coli Infections - therapy
Genome, Viral
Genotype
Life Sciences
Mice
Microbial Viability
Microbiology and Parasitology
Phage Therapy - methods
Sequence Analysis, DNA
title Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex
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