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

Identifieur interne : 000071 ( Hal/Corpus ); précédent : 000070; suivant : 000072

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

Auteurs : Nicolas Dufour ; Olivier Clermont ; Béatrice La Combe ; Jonathan Messika ; Sara Dion ; Varun Khanna ; Erick Denamur ; Jean-Damien Ricard ; Laurent Debarbieux

Source :

RBID : Hal:pasteur-01539016

English descriptors

Abstract

OBJECTIVES: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.METHODS: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.RESULTS: 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.CONCLUSION: 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.


Url:
DOI: 10.1093/jac/dkw253

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Hal:pasteur-01539016

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<name sortKey="Debarbieux, Laurent" sort="Debarbieux, Laurent" uniqKey="Debarbieux L" first="Laurent" last="Debarbieux">Laurent Debarbieux</name>
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<idno type="DOI">10.1093/jac/dkw253</idno>
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<title level="j">Journal of Antimicrobial Chemotherapy</title>
<idno type="ISSN">0305-7453</idno>
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<date type="datePub">2016-11</date>
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<term>23 bacteriophage</term>
<term>Escherichia coli</term>
<term>T131 -O25b:H4</term>
<term>antibiotic resistance</term>
<term>extended spectrum beta-lactamase</term>
<term>phage therapy</term>
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<p>OBJECTIVES: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.METHODS: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.RESULTS: 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.CONCLUSION: 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.</p>
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<title xml:lang="en">Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex.</title>
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<forename type="first">Nicolas</forename>
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<surname>Debarbieux</surname>
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<surname>Debarbieux</surname>
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<email type="md5">57d04d2b8f1e414bb238ff02e0295383</email>
<email type="domain">pasteur.fr</email>
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<funder>This project was supported by a joint research grant from both Institut Pasteur and Assistance Publique–Hôpitaux de Paris (Programme Transversal de Recherche #417 and Poste d′Accueil pour praticien hospitalier).</funder>
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<date type="whenSubmitted">2017-06-14 12:01:14</date>
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<idno type="stamp" n="PASTEUR">Institut Pasteur</idno>
<idno type="stamp" n="UNIV-PARIS7" corresp="UNIV-PARIS">Université Denis Diderot - Paris VII</idno>
<idno type="stamp" n="APHP" corresp="INSERM">AP-HP</idno>
<idno type="stamp" n="UNIV-PARIS13">Université Paris-Nord - Paris XIII </idno>
<idno type="stamp" n="USPC">Université Sorbonne Paris Cité</idno>
<idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno>
<idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
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<idno type="stamp" n="SORBONNE-PARIS-NORD">Université Sorbonne Paris Nord</idno>
<idno type="stamp" n="UNIV-PARIS">Université de Paris</idno>
<idno type="stamp" n="UP-SANTE">Université de Paris - Faculté de Santé</idno>
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<title xml:lang="en">Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex.</title>
<author role="aut">
<persName>
<forename type="first">Nicolas</forename>
<surname>Dufour</surname>
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<author role="aut">
<persName>
<forename type="first">Olivier</forename>
<surname>Clermont</surname>
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<idno type="halauthorid">408953</idno>
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</author>
<author role="aut">
<persName>
<forename type="first">Béatrice</forename>
<surname>La Combe</surname>
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<idno type="halauthorid">1558587</idno>
<affiliation ref="#struct-247341"></affiliation>
<affiliation ref="#struct-457457"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Jonathan</forename>
<surname>Messika</surname>
</persName>
<idno type="halauthorid">1235513</idno>
<affiliation ref="#struct-457457"></affiliation>
<affiliation ref="#struct-247341"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Sara</forename>
<surname>Dion</surname>
</persName>
<idno type="halauthorid">397005</idno>
<affiliation ref="#struct-247341"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Varun</forename>
<surname>Khanna</surname>
</persName>
<idno type="halauthorid">1128107</idno>
<affiliation ref="#struct-463018"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Erick</forename>
<surname>Denamur</surname>
</persName>
<idno type="halauthorid">566790</idno>
<affiliation ref="#struct-349749"></affiliation>
<affiliation ref="#struct-247341"></affiliation>
</author>
<author role="aut">
<persName>
<forename type="first">Jean-Damien</forename>
<surname>Ricard</surname>
</persName>
<idno type="halauthorid">467405</idno>
<affiliation ref="#struct-247341"></affiliation>
<affiliation ref="#struct-457457"></affiliation>
</author>
<author role="crp">
<persName>
<forename type="first">Laurent</forename>
<surname>Debarbieux</surname>
</persName>
<email type="md5">57d04d2b8f1e414bb238ff02e0295383</email>
<email type="domain">pasteur.fr</email>
<idno type="idhal" notation="string">laurent-debarbieux</idno>
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<idno type="halJournalId" status="VALID">15068</idno>
<idno type="issn">0305-7453</idno>
<idno type="eissn">1460-2091</idno>
<title level="j">Journal of Antimicrobial Chemotherapy</title>
<imprint>
<publisher>Oxford University Press (OUP)</publisher>
<biblScope unit="volume">71</biblScope>
<biblScope unit="issue">11</biblScope>
<biblScope unit="pp">3072-3080</biblScope>
<date type="datePub">2016-11</date>
<date type="dateEpub">2016-07-07</date>
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<idno type="doi">10.1093/jac/dkw253</idno>
<idno type="pubmed">27387322</idno>
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<language ident="en">English</language>
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<textClass>
<keywords scheme="author">
<term xml:lang="en">T131 -O25b:H4</term>
<term xml:lang="en">Escherichia coli</term>
<term xml:lang="en">antibiotic resistance</term>
<term xml:lang="en">phage therapy</term>
<term xml:lang="en">23 bacteriophage</term>
<term xml:lang="en">extended spectrum beta-lactamase</term>
</keywords>
<classCode scheme="halDomain" n="sdv.mp.bac">Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology</classCode>
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<abstract xml:lang="0">
<p>OBJECTIVES: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.METHODS: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.RESULTS: 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.CONCLUSION: 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.</p>
</abstract>
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