Common Evolutionary Origin for the Unstable Virulence Plasmid pMUM Found in Geographically Diverse Strains of Mycobacterium ulcerans
Identifieur interne : 001004 ( Pmc/Corpus ); précédent : 001003; suivant : 001005Common Evolutionary Origin for the Unstable Virulence Plasmid pMUM Found in Geographically Diverse Strains of Mycobacterium ulcerans
Auteurs : Timothy P. Stinear ; Hui Hong ; Wafa Frigui ; Melinda J. Pryor ; Roland Brosch ; Thierry Garnier ; Peter F. Leadlay ; Stewart T. ColeSource :
- Journal of Bacteriology [ 0021-9193 ] ; 2005.
Abstract
The 174-kb virulence plasmid pMUM001 in
Url:
DOI: 10.1128/JB.187.5.1668-1676.2005
PubMed: 15716437
PubMed Central: 1064021
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PMC:1064021Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Common Evolutionary Origin for the Unstable Virulence Plasmid pMUM Found in Geographically Diverse Strains of <italic>Mycobacterium ulcerans</italic>
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<author><name sortKey="Stinear, Timothy P" sort="Stinear, Timothy P" uniqKey="Stinear T" first="Timothy P." last="Stinear">Timothy P. Stinear</name>
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<author><name sortKey="Hong, Hui" sort="Hong, Hui" uniqKey="Hong H" first="Hui" last="Hong">Hui Hong</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="Pryor, Melinda J" sort="Pryor, Melinda J" uniqKey="Pryor M" first="Melinda J." last="Pryor">Melinda J. Pryor</name>
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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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<series><title level="j">Journal of Bacteriology</title>
<idno type="ISSN">0021-9193</idno>
<idno type="eISSN">1098-5530</idno>
<imprint><date when="2005">2005</date>
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<front><div type="abstract" xml:lang="en"><p>The 174-kb virulence plasmid pMUM001 in <italic>Mycobacterium ulcerans</italic>
epidemic strain Agy99 harbors three very large and homologous genes that encode giant polyketide synthases (PKS) responsible for the synthesis of the lipid toxin mycolactone. Deeper investigation of <italic>M. ulcerans</italic>
Agy99 resulted in identification of two types of spontaneous deletion variants of pMUM001 within a population of cells that also contained the intact plasmid. These variants arose from recombination between two 8-kb sections of the same plasmid sequence, resulting in the loss of a 65-kb region bearing two of the three mycolactone PKS genes. Investigation of nine diverse <italic>M. ulcerans</italic>
strains by using PCR and Southern hybridization for eight pMUM001 gene sequences confirmed the presence of pMUM001-like elements (collectively called pMUM) in all <italic>M. ulcerans</italic>
strains. Physical mapping of these plasmids revealed that like <italic>M. ulcerans</italic>
Agy99, three strains had undergone major deletions in their mycolactone PKS loci. Online liquid chromatography-sequential mass spectrometry analysis of lipid extracts confirmed that strains with PKS deletions were unable to produce mycolactone or any related cometabolites. Interstrain comparisons of the plasmid gene sequences revealed greater than 98% nucleotide identity, and the phylogeny inferred from these sequences closely mimicked the phylogeny from a previous multilocus sequence typing study in which chromosomally encoded loci were used, a result that is consistent with the hypothesis that <italic>M. ulcerans</italic>
diverged from the closely related organism <italic>Mycobacterium marinum</italic>
by acquiring pMUM. Our results suggest that pMUM is a defining characteristic of <italic>M. ulcerans</italic>
but that in the absence of purifying selection, deletion of plasmid sequences and a corresponding loss of mycolactone production readily arise.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Bacteriol</journal-id>
<journal-id journal-id-type="publisher-id">jb</journal-id>
<journal-title>Journal of Bacteriology</journal-title>
<issn pub-type="ppub">0021-9193</issn>
<issn pub-type="epub">1098-5530</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">15716437</article-id>
<article-id pub-id-type="pmc">1064021</article-id>
<article-id pub-id-type="publisher-id">1458-04</article-id>
<article-id pub-id-type="doi">10.1128/JB.187.5.1668-1676.2005</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Bacteriophages, Transposons, and Plasmids</subject>
</subj-group>
</article-categories>
<title-group><article-title>Common Evolutionary Origin for the Unstable Virulence Plasmid pMUM Found in Geographically Diverse Strains of <italic>Mycobacterium ulcerans</italic>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Stinear</surname>
<given-names>Timothy P.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff1">2</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hong</surname>
<given-names>Hui</given-names>
</name>
<xref ref-type="aff" rid="aff1">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Frigui</surname>
<given-names>Wafa</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pryor</surname>
<given-names>Melinda J.</given-names>
</name>
<xref ref-type="aff" rid="aff1">4</xref>
<xref ref-type="fn" rid="fn1">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brosch</surname>
<given-names>Roland</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Garnier</surname>
<given-names>Thierry</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Leadlay</surname>
<given-names>Peter F.</given-names>
</name>
<xref ref-type="aff" rid="aff1">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cole</surname>
<given-names>Stewart T.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
</contrib-group>
<aff id="aff1">Unité de Génétique Moléculaire Bactérienne,<label>1</label>
Plate-Forme 4-Intégration et Analyse Génomiques, Génopole, Institut Pasteur, Paris, France,<label>4</label>
Department of Microbiology, Monash University, Clayton, Australia,<label>2</label>
Department of Chemistry,<label>3</label>
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom<label>5</label>
</aff>
<author-notes><fn id="cor1"><label>*</label>
<p>Corresponding author. Present address: Department of Microbiology, Monash University, Wellington Road, Clayton 3800, Australia. Phone: 61-3-99059709. Fax: 61-3-99054811. E-mail: <email>tim.stinear@med.monash.edu.au</email>
.</p>
</fn>
<fn id="fn1"><label>†</label>
<p>Present address: Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Australia.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>3</month>
<year>2005</year>
</pub-date>
<volume>187</volume>
<issue>5</issue>
<fpage>1668</fpage>
<lpage>1676</lpage>
<history><date date-type="received"><day>8</day>
<month>10</month>
<year>2004</year>
</date>
<date date-type="accepted"><day>29</day>
<month>11</month>
<year>2004</year>
</date>
</history>
<copyright-statement>Copyright © 2005, American Society for Microbiology</copyright-statement>
<copyright-year>2005</copyright-year>
<abstract><p>The 174-kb virulence plasmid pMUM001 in <italic>Mycobacterium ulcerans</italic>
epidemic strain Agy99 harbors three very large and homologous genes that encode giant polyketide synthases (PKS) responsible for the synthesis of the lipid toxin mycolactone. Deeper investigation of <italic>M. ulcerans</italic>
Agy99 resulted in identification of two types of spontaneous deletion variants of pMUM001 within a population of cells that also contained the intact plasmid. These variants arose from recombination between two 8-kb sections of the same plasmid sequence, resulting in the loss of a 65-kb region bearing two of the three mycolactone PKS genes. Investigation of nine diverse <italic>M. ulcerans</italic>
strains by using PCR and Southern hybridization for eight pMUM001 gene sequences confirmed the presence of pMUM001-like elements (collectively called pMUM) in all <italic>M. ulcerans</italic>
strains. Physical mapping of these plasmids revealed that like <italic>M. ulcerans</italic>
Agy99, three strains had undergone major deletions in their mycolactone PKS loci. Online liquid chromatography-sequential mass spectrometry analysis of lipid extracts confirmed that strains with PKS deletions were unable to produce mycolactone or any related cometabolites. Interstrain comparisons of the plasmid gene sequences revealed greater than 98% nucleotide identity, and the phylogeny inferred from these sequences closely mimicked the phylogeny from a previous multilocus sequence typing study in which chromosomally encoded loci were used, a result that is consistent with the hypothesis that <italic>M. ulcerans</italic>
diverged from the closely related organism <italic>Mycobacterium marinum</italic>
by acquiring pMUM. Our results suggest that pMUM is a defining characteristic of <italic>M. ulcerans</italic>
but that in the absence of purifying selection, deletion of plasmid sequences and a corresponding loss of mycolactone production readily arise.</p>
</abstract>
</article-meta>
</front>
</pmc>
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