PandemieGrippaleV1, Main, Exploration, bibRecordById, Hal:pasteur-02618562

The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on the virulence of Mycobacterium tuberculosis

Identifieur interne : 000807 ( Main/Exploration ); précédent : 000806; suivant : 000808

The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on the virulence of Mycobacterium tuberculosis

Auteurs : Nawel Slama [France] ; Stevie Jamet [France] ; Wafa Frigui [France] ; Alexandre Pawlik [France] ; Daria Bottai [France] ; Françoise Laval [France] ; Patricia Constant [France] ; Anne Lemassu [France] ; Kaymeuang Cam [France] ; Mamadou Daffé [France] ; Roland Brosch [France] ; Nathalie Eynard [France] ; Annaïk Quémard [France]

Source :

Molecular Microbiology [ 0950-382X ] ; 2016-02.

RBID : Hal:pasteur-02618562

Abstract

Understanding the molecular strategies used by Mycobacterium tuberculosis to invade and persist within the host is of paramount importance to tackle the tuberculosis pandemic. Comparative genomic surveys have revealed that hadC, encoding a subunit of the HadBC dehydratase, is mutated in the avirulent M. tuberculosis H37Ra strain. We show here that mutation or deletion of hadC affects the biosynthesis of oxygenated mycolic acids, substantially reducing their production level. Additionally, it causes the loss of atypical extra-long mycolic acids, demonstrating the involvement of HadBC in the late elongation steps of mycolic acid biosynthesis. These events have an impact on the morphotype, cording capacity and biofilm growth of the bacilli as well as on their sensitivity to agents such as rifampicin. Furthermore, deletion of hadC leads to a dramatic loss of virulence: an almost 4-log drop of the bacterial load in the lungs and spleens of infected immunodeficient mice. Both its unique function and importance for M. tuberculosis virulence make HadBC an attractive therapeutic target for tuberculosis drug development.

Url:

https://hal-pasteur.archives-ouvertes.fr/pasteur-02618562

DOI: 10.1111/mmi.13266

Affiliations:

France

Links toward previous steps (curation, corpus...)

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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en">The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on the virulence of Mycobacterium tuberculosis</title>
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<author><name sortKey="Jamet, Stevie" sort="Jamet, Stevie" uniqKey="Jamet S" first="Stevie" last="Jamet">Stevie Jamet</name>
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<author><name sortKey="Frigui, Wafa" sort="Frigui, Wafa" uniqKey="Frigui W" first="Wafa" last="Frigui">Wafa Frigui</name>
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<author><name sortKey="Cam, Kaymeuang" sort="Cam, Kaymeuang" uniqKey="Cam K" first="Kaymeuang" last="Cam">Kaymeuang Cam</name>
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<author><name sortKey="Daffe, Mamadou" sort="Daffe, Mamadou" uniqKey="Daffe M" first="Mamadou" last="Daffé">Mamadou Daffé</name>
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<country>France</country>
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<author><name sortKey="Brosch, Roland" sort="Brosch, Roland" uniqKey="Brosch R" first="Roland" last="Brosch">Roland Brosch</name>
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          <orgName>Institut Pasteur [Paris]</orgName>
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</author>
<author><name sortKey="Eynard, Nathalie" sort="Eynard, Nathalie" uniqKey="Eynard N" first="Nathalie" last="Eynard">Nathalie Eynard</name>
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<country>France</country>
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</author>
<author><name sortKey="Quemard, Annaik" sort="Quemard, Annaik" uniqKey="Quemard A" first="Annaïk" last="Quémard">Annaïk Quémard</name>
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          <idno type="ISNI">0000 0000 9679 268X</idno>
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          <orgName>Institut de pharmacologie et de biologie structurale</orgName>
          <orgName type="acronym">IPBS</orgName>
          <date type="start">1996-01-01</date>
          <desc>            <address>              <addrLine>205 Route de Narbonne 31077 TOULOUSE CEDEX 4</addrLine>
              <country key="FR"></country>
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          <idno type="ISNI">0000000121617331</idno>
          <orgName>Université Toulouse III - Paul Sabatier</orgName>
          <orgName type="acronym">UT3</orgName>
          <desc>            <address>              <addrLine>118 route de Narbonne - 31062 Toulouse</addrLine>
              <country key="FR"></country>
            </address>
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          <desc>            <address>              <addrLine>41 Allée Jules Guesde, 31000 Toulouse</addrLine>
              <country key="FR"></country>
            </address>
          </desc>
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</tutelle>
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          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
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            </address>
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<country>France</country>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1111/mmi.13266</idno>
<series><title level="j">Molecular Microbiology</title>
<idno type="ISSN">0950-382X</idno>
<imprint><date type="datePub">2016-02</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en">              <p>Understanding the molecular strategies used by Mycobacterium tuberculosis to invade and persist within the host is of paramount importance to tackle the tuberculosis pandemic. Comparative genomic surveys have revealed that hadC, encoding a subunit of the HadBC dehydratase, is mutated in the avirulent M. tuberculosis H37Ra strain. We show here that mutation or deletion of hadC affects the biosynthesis of oxygenated mycolic acids, substantially reducing their production level. Additionally, it causes the loss of atypical extra-long mycolic acids, demonstrating the involvement of HadBC in the late elongation steps of mycolic acid biosynthesis. These events have an impact on the morphotype, cording capacity and biofilm growth of the bacilli as well as on their sensitivity to agents such as rifampicin. Furthermore, deletion of hadC leads to a dramatic loss of virulence: an almost 4-log drop of the bacterial load in the lungs and spleens of infected immunodeficient mice. Both its unique function and importance for M. tuberculosis virulence make HadBC an attractive therapeutic target for tuberculosis drug development.</p>
            </div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
</country>
</list>
<tree><country name="France"><noRegion><name sortKey="Slama, Nawel" sort="Slama, Nawel" uniqKey="Slama N" first="Nawel" last="Slama">Nawel Slama</name>
</noRegion>
<name sortKey="Bottai, Daria" sort="Bottai, Daria" uniqKey="Bottai D" first="Daria" last="Bottai">Daria Bottai</name>
<name sortKey="Brosch, Roland" sort="Brosch, Roland" uniqKey="Brosch R" first="Roland" last="Brosch">Roland Brosch</name>
<name sortKey="Cam, Kaymeuang" sort="Cam, Kaymeuang" uniqKey="Cam K" first="Kaymeuang" last="Cam">Kaymeuang Cam</name>
<name sortKey="Constant, Patricia" sort="Constant, Patricia" uniqKey="Constant P" first="Patricia" last="Constant">Patricia Constant</name>
<name sortKey="Daffe, Mamadou" sort="Daffe, Mamadou" uniqKey="Daffe M" first="Mamadou" last="Daffé">Mamadou Daffé</name>
<name sortKey="Eynard, Nathalie" sort="Eynard, Nathalie" uniqKey="Eynard N" first="Nathalie" last="Eynard">Nathalie Eynard</name>
<name sortKey="Frigui, Wafa" sort="Frigui, Wafa" uniqKey="Frigui W" first="Wafa" last="Frigui">Wafa Frigui</name>
<name sortKey="Jamet, Stevie" sort="Jamet, Stevie" uniqKey="Jamet S" first="Stevie" last="Jamet">Stevie Jamet</name>
<name sortKey="Laval, Francoise" sort="Laval, Francoise" uniqKey="Laval F" first="Françoise" last="Laval">Françoise Laval</name>
<name sortKey="Lemassu, Anne" sort="Lemassu, Anne" uniqKey="Lemassu A" first="Anne" last="Lemassu">Anne Lemassu</name>
<name sortKey="Pawlik, Alexandre" sort="Pawlik, Alexandre" uniqKey="Pawlik A" first="Alexandre" last="Pawlik">Alexandre Pawlik</name>
<name sortKey="Quemard, Annaik" sort="Quemard, Annaik" uniqKey="Quemard A" first="Annaïk" last="Quémard">Annaïk Quémard</name>
</country>
</tree>
</affiliations>
</record>

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The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on the virulence of Mycobacterium tuberculosis

The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on the virulence of Mycobacterium tuberculosis

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