<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-02283128</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-19T06:41:00+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">Changes in Intrinsic Antibiotic Susceptibility during a Long-Term Evolution Experiment with Escherichia coli</title>
            <author role="aut">
              <persName>
                <forename type="first">Otmane</forename>
                <surname>Lamrabet</surname>
              </persName>
              <idno type="halauthorid">715533-0</idno>
              <affiliation ref="#struct-707"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Mikaël</forename>
                <surname>Martin</surname>
              </persName>
              <idno type="halauthorid">889061-0</idno>
              <affiliation ref="#struct-1042067"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Richard</forename>
                <surname>Lenski</surname>
              </persName>
              <idno type="halauthorid">1649152-0</idno>
              <affiliation ref="#struct-465190"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Dominique</forename>
                <surname>Schneider</surname>
              </persName>
              <idno type="idhal" notation="numeric">756490</idno>
              <idno type="halauthorid" notation="string">1621-756490</idno>
              <idno type="IDREF">https://www.idref.fr/112471048</idno>
              <affiliation ref="#struct-1042067"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Catherine</forename>
                <surname>ZOPPIS</surname>
              </persName>
              <email type="md5">6dd921a6b2d3ffcc35d48c9c0d521def</email>
              <email type="domain">univ-grenoble-alpes.fr</email>
            </editor>
          </titleStmt>
          <editionStmt>
            <edition n="v1" type="current">
              <date type="whenSubmitted">2019-09-10 14:56:08</date>
              <date type="whenModified">2025-09-27 19:26:48</date>
              <date type="whenReleased">2019-09-10 14:56:08</date>
              <date type="whenProduced">2019-04-30</date>
              <ref type="externalLink" target="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401480"/>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="469462">
                <persName>
                  <forename>Catherine</forename>
                  <surname>ZOPPIS</surname>
                </persName>
                <email type="md5">6dd921a6b2d3ffcc35d48c9c0d521def</email>
                <email type="domain">univ-grenoble-alpes.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-02283128</idno>
            <idno type="halUri">https://hal.science/hal-02283128</idno>
            <idno type="halBibtex">lamrabet:hal-02283128</idno>
            <idno type="halRefHtml">&lt;i&gt;mBio&lt;/i&gt;, 2019, 10 (2), &lt;a target="_blank" href="https://dx.doi.org/10.1128/mBio.00189-19"&gt;&amp;#x27E8;10.1128/mBio.00189-19&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">mBio, 2019, 10 (2), &amp;#x27E8;10.1128/mBio.00189-19&amp;#x27E9;</idno>
            <availability status="restricted"/>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="UGA">HAL Grenoble Alpes</idno>
            <idno type="stamp" n="IMAG">IMAG</idno>
            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="INPG">Institut polytechnique de Grenoble</idno>
            <idno type="stamp" n="TIMC-IMAG">TIMC</idno>
            <idno type="stamp" n="TIMC-IMAG-GEM" corresp="TIMC-IMAG">Génomique et Évolution des Microorganismes </idno>
            <idno type="stamp" n="UNIV-LYON">Université de Lyon</idno>
            <idno type="stamp" n="UGA-COMUE">Université Grenoble Alpes [2016-2019]</idno>
            <idno type="stamp" n="TIMC-TREE" corresp="TIMC-IMAG">TrEE : Translational microbial Evolution and Engineering</idno>
            <idno type="stamp" n="TEST3-HALCNRS">TEST3-HALCNRS</idno>
            <idno type="stamp" n="TEST-UGA">TEST-UGA</idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">Changes in Intrinsic Antibiotic Susceptibility during a Long-Term Evolution Experiment with Escherichia coli</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Otmane</forename>
                    <surname>Lamrabet</surname>
                  </persName>
                  <idno type="halauthorid">715533-0</idno>
                  <affiliation ref="#struct-707"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Mikaël</forename>
                    <surname>Martin</surname>
                  </persName>
                  <idno type="halauthorid">889061-0</idno>
                  <affiliation ref="#struct-1042067"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Richard</forename>
                    <surname>Lenski</surname>
                  </persName>
                  <idno type="halauthorid">1649152-0</idno>
                  <affiliation ref="#struct-465190"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Dominique</forename>
                    <surname>Schneider</surname>
                  </persName>
                  <idno type="idhal" notation="numeric">756490</idno>
                  <idno type="halauthorid" notation="string">1621-756490</idno>
                  <idno type="IDREF">https://www.idref.fr/112471048</idno>
                  <affiliation ref="#struct-1042067"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">159780</idno>
                <idno type="issn">2161-2129</idno>
                <idno type="eissn">2150-7511</idno>
                <title level="j">mBio</title>
                <imprint>
                  <publisher> American Society for Microbiology</publisher>
                  <biblScope unit="volume">10</biblScope>
                  <biblScope unit="issue">2</biblScope>
                  <date type="datePub">2019-04-30</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1128/mBio.00189-19</idno>
              <idno type="pubmedcentral">PMC6401480</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <keywords scheme="author">
                <term xml:lang="en">pleiotropy</term>
                <term xml:lang="en">mutation accumulation</term>
                <term xml:lang="en">evolution</term>
                <term xml:lang="en">antibiotic resistance</term>
                <term xml:lang="en">Escherichia coli</term>
              </keywords>
              <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>High-level resistance often evolves when populations of bacteria are exposed to antibiotics, by either mutations or horizontally acquired genes. There is also variation in the intrinsic resistance levels of different bacterial strains and species that is not associated with any known history of exposure. In many cases, evolved resistance is costly to the bacteria, such that resistant types have lower fitness than their progenitors in the absence of antibiotics. Some longer-term studies have shown that bacteria often evolve compensatory changes that overcome these tradeoffs, but even those studies have typically lasted only a few hundred generations. In this study, we examine changes in the susceptibilities of 12 populations of Escherichia coli to 15 antibiotics after 2,000 and 50,000 generations without exposure to any antibiotic. On average, the evolved bacteria were more susceptible to most antibiotics than was their ancestor. The bacteria at 50,000 generations tended to be even more susceptible than after 2,000 generations, although most of the change occurred during the first 2,000 generations. Despite the general trend toward increased susceptibility, we saw diverse outcomes with different antibiotics. For streptomycin, which was the only drug to which the ancestral strain was highly resistant, none of the evolved lines showed any increased susceptibility. The independently evolved lineages often exhibited correlated responses to the antibiotics, with correlations usually corresponding to their modes of action. On balance, our study shows that bacteria with low levels of intrinsic resistance often evolve to become even more susceptible to antibiotics in the absence of corresponding selection.IMPORTANCE Resistance to antibiotics often evolves when bacteria encounter antibiotics. However, bacterial strains and species without any known exposure to these drugs also vary in their intrinsic susceptibility. In many cases, evolved resistance has been shown to be costly to the bacteria, such that resistant types have reduced competitiveness relative to their sensitive progenitors in the absence of antibiotics. In this study, we examined changes in the susceptibilities of 12 populations of Escherichia coli to 15 antibiotics after 2,000 and 50,000 generations without exposure to any drug. The evolved bacteria tended to become more susceptible to most antibiotics, with most of the change occurring during the first 2,000 generations, when the bacteria were undergoing rapid adaptation to their experimental conditions. On balance, our findings indicate that bacteria with low levels of intrinsic resistance can, in the absence of relevant selection, become even more susceptible to antibiotics.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="laboratory" xml:id="struct-707" status="OLD">
          <idno type="IdRef">14728936X</idno>
          <idno type="ISNI">0000 0004 4687 1979</idno>
          <idno type="RNSR">199511969L</idno>
          <idno type="ROR">https://ror.org/03985kf35</idno>
          <orgName>Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525</orgName>
          <orgName type="acronym">TIMC-IMAG</orgName>
          <date type="start">1993-01-01</date>
          <date type="end">2015-12-31</date>
          <desc>
            <address>
              <addrLine>Domaine de la Merci, 38706 La Tronche, France</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www-timc.imag.fr</ref>
          </desc>
          <listRelation>
            <relation active="#struct-51016" type="direct"/>
            <relation active="#struct-89889" type="direct"/>
            <relation active="#struct-301767" type="direct"/>
            <relation name="UMR5525" active="#struct-441569" type="direct"/>
          </listRelation>
        </org>
        <org type="researchteam" xml:id="struct-1042067" status="OLD">
          <orgName>Génomique et Évolution des Microorganismes</orgName>
          <orgName type="acronym">TIMC-IMAG-GEM</orgName>
          <date type="start">2016-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <addrLine>Domaine de la Merci, 38706 La Tronche, France</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www-timc.imag.fr/GEM</ref>
          </desc>
          <listRelation>
            <relation active="#struct-1042061" type="direct"/>
            <relation active="#struct-89889" type="indirect"/>
            <relation active="#struct-301767" type="indirect"/>
            <relation name="UMR5525" active="#struct-441569" type="indirect"/>
            <relation active="#struct-445543" type="indirect"/>
          </listRelation>
        </org>
        <org type="laboratory" xml:id="struct-465190" status="INCOMING">
          <orgName>Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 USA</orgName>
          <desc>
            <address>
              <country key="US"/>
            </address>
          </desc>
          <listRelation>
            <relation active="#struct-235550" type="direct"/>
            <relation active="#struct-566438" type="indirect"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-51016" status="OLD">
          <idno type="IdRef">026404796</idno>
          <idno type="ROR">https://ror.org/02aj0kh94</idno>
          <orgName>Université Joseph Fourier - Grenoble 1</orgName>
          <orgName type="acronym">UJF</orgName>
          <date type="end">2015-12-31</date>
          <desc>
            <address>
              <addrLine>BP 53 - 38041 Grenoble Cedex 9</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.ujf-grenoble.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-89889" status="OLD">
          <idno type="IdRef">026388804</idno>
          <idno type="ROR">https://ror.org/05sbt2524</idno>
          <orgName>Institut polytechnique de Grenoble - Grenoble Institute of Technology</orgName>
          <orgName type="acronym">Grenoble INP</orgName>
          <date type="start">2007-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <addrLine>46 avenue Félix Viallet 38031 Grenoble Cedex 1</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.grenoble-inp.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-301767" status="VALID">
          <idno type="ROR">https://ror.org/01c7wz417</idno>
          <orgName>VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement</orgName>
          <orgName type="acronym">VAS</orgName>
          <date type="start">2010-01-01</date>
          <desc>
            <address>
              <addrLine>Université de Lyon, VetAgro Sup, 69280 Marcy l'Etoile (campus vétérinaire); Université de Clermont, VetAgro Sup, 63370 Lempdes (campus agronomique)</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.vetagro-sup.fr/</ref>
          </desc>
        </org>
        <org type="regroupinstitution" xml:id="struct-441569" status="VALID">
          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <idno type="ROR">https://ror.org/02feahw73</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.cnrs.fr/</ref>
          </desc>
        </org>
        <org type="laboratory" xml:id="struct-1042061" status="OLD">
          <idno type="IdRef">14728936X</idno>
          <idno type="ISNI">0000 0004 4687 1979</idno>
          <idno type="RNSR">199511969L</idno>
          <idno type="ROR">https://ror.org/03985kf35</idno>
          <orgName>Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525</orgName>
          <orgName type="acronym">TIMC-IMAG</orgName>
          <date type="start">2016-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <addrLine>Domaine de la Merci, 38706 La Tronche, France</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www-timc.imag.fr</ref>
          </desc>
          <listRelation>
            <relation active="#struct-89889" type="direct"/>
            <relation active="#struct-301767" type="direct"/>
            <relation name="UMR5525" active="#struct-441569" type="direct"/>
            <relation active="#struct-445543" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-445543" status="OLD">
          <idno type="IdRef">188399275</idno>
          <idno type="ROR">https://ror.org/02rx3b187</idno>
          <orgName>Université Grenoble Alpes [2016-2019]</orgName>
          <orgName type="acronym">UGA [2016-2019]</orgName>
          <date type="start">2016-01-01</date>
          <date type="end">2019-12-31</date>
          <desc>
            <address>
              <addrLine>38058 Grenoble cedex</addrLine>
              <country key="FR"/>
            </address>
          </desc>
        </org>
        <org type="institution" xml:id="struct-235550" status="VALID">
          <idno type="ROR">https://ror.org/05hs6h993</idno>
          <orgName>Michigan State University [East Lansing]</orgName>
          <desc>
            <address>
              <addrLine>220 Trowbridge Rd East Lansing, MI 48824</addrLine>
              <country key="US"/>
            </address>
            <ref type="url">https://msu.edu/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-566438" type="direct"/>
          </listRelation>
        </org>
        <org type="regroupinstitution" xml:id="struct-566438" status="VALID">
          <idno type="ROR">https://ror.org/05hs6h993</idno>
          <orgName>Michigan State University System</orgName>
          <desc>
            <address>
              <addrLine>Michigan</addrLine>
              <country key="US"/>
            </address>
            <ref type="url">https://msu.edu/</ref>
          </desc>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>