Serological Evaluation of Mycobacterium ulcerans Antigens Identified by Comparative Genomics
Identifieur interne : 002776 ( Pmc/Curation ); précédent : 002775; suivant : 002777Serological Evaluation of Mycobacterium ulcerans Antigens Identified by Comparative Genomics
Auteurs : Sacha J. Pidot [Australie] ; Jessica L. Porter [Australie] ; Laurent Marsollier [France] ; Annick Chauty [Bénin] ; Florence Migot-Nabias [France] ; Cyril Badaut [France] ; Angèle Bénard [Suisse] ; Marie-Therese Ruf [Suisse] ; Torsten Seemann [Australie] ; Paul D. R. Johnson [Australie] ; John K. Davies [Australie] ; Grant A. Jenkin [Australie] ; Gerd Pluschke [Suisse] ; Timothy P. Stinear [Australie]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2010.
Abstract
A specific and sensitive serodiagnostic test for
Url:
DOI: 10.1371/journal.pntd.0000872
PubMed: 21072233
PubMed Central: 2970529
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PMC:2970529Le document en format XML
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Antigens Identified by Comparative Genomics</title>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology, Monash University, Clayton, Victoria</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia</addr-line>
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<author><name sortKey="Chauty, Annick" sort="Chauty, Annick" uniqKey="Chauty A" first="Annick" last="Chauty">Annick Chauty</name>
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<author><name sortKey="Migot Nabias, Florence" sort="Migot Nabias, Florence" uniqKey="Migot Nabias F" first="Florence" last="Migot-Nabias">Florence Migot-Nabias</name>
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<author><name sortKey="Badaut, Cyril" sort="Badaut, Cyril" uniqKey="Badaut C" first="Cyril" last="Badaut">Cyril Badaut</name>
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<author><name sortKey="Ruf, Marie Therese" sort="Ruf, Marie Therese" uniqKey="Ruf M" first="Marie-Therese" last="Ruf">Marie-Therese Ruf</name>
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<author><name sortKey="Seemann, Torsten" sort="Seemann, Torsten" uniqKey="Seemann T" first="Torsten" last="Seemann">Torsten Seemann</name>
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<author><name sortKey="Johnson, Paul D R" sort="Johnson, Paul D R" uniqKey="Johnson P" first="Paul D. R." last="Johnson">Paul D. R. Johnson</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Serological Evaluation of <italic>Mycobacterium ulcerans</italic>
Antigens Identified by Comparative Genomics</title>
<author><name sortKey="Pidot, Sacha J" sort="Pidot, Sacha J" uniqKey="Pidot S" first="Sacha J." last="Pidot">Sacha J. Pidot</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Monash University, Clayton, Victoria, Australia</addr-line>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology, Monash University, Clayton, Victoria</wicri:regionArea>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria</wicri:regionArea>
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<author><name sortKey="Porter, Jessica L" sort="Porter, Jessica L" uniqKey="Porter J" first="Jessica L." last="Porter">Jessica L. Porter</name>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
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<author><name sortKey="Marsollier, Laurent" sort="Marsollier, Laurent" uniqKey="Marsollier L" first="Laurent" last="Marsollier">Laurent Marsollier</name>
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</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Groupe d'Étude des Interactions Hôte-Pathogène, Université d'Angers, Angers</wicri:regionArea>
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<author><name sortKey="Chauty, Annick" sort="Chauty, Annick" uniqKey="Chauty A" first="Annick" last="Chauty">Annick Chauty</name>
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</nlm:aff>
<country xml:lang="fr">Bénin</country>
<wicri:regionArea>Centre de Dépistage et de Traitement de l'ulcère de Buruli, Pobè</wicri:regionArea>
</affiliation>
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<author><name sortKey="Migot Nabias, Florence" sort="Migot Nabias, Florence" uniqKey="Migot Nabias F" first="Florence" last="Migot-Nabias">Florence Migot-Nabias</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Institut de Recherche pour le Développement UMR216, Mère et enfant face aux infections tropicales, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut de Recherche pour le Développement UMR216, Mère et enfant face aux infections tropicales, Paris</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Faculté de Pharmacie, Université Paris Descartes, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Faculté de Pharmacie, Université Paris Descartes, Paris</wicri:regionArea>
</affiliation>
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<author><name sortKey="Badaut, Cyril" sort="Badaut, Cyril" uniqKey="Badaut C" first="Cyril" last="Badaut">Cyril Badaut</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Institut de Recherche pour le Développement UMR216, Mère et enfant face aux infections tropicales, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut de Recherche pour le Développement UMR216, Mère et enfant face aux infections tropicales, Paris</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff6"><addr-line>Faculté de Pharmacie, Université Paris Descartes, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Faculté de Pharmacie, Université Paris Descartes, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Benard, Angele" sort="Benard, Angele" uniqKey="Benard A" first="Angèle" last="Bénard">Angèle Bénard</name>
<affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>Swiss Tropical Public Health Institute, Basel, Switzerland</addr-line>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Swiss Tropical Public Health Institute, Basel</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ruf, Marie Therese" sort="Ruf, Marie Therese" uniqKey="Ruf M" first="Marie-Therese" last="Ruf">Marie-Therese Ruf</name>
<affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>Swiss Tropical Public Health Institute, Basel, Switzerland</addr-line>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Swiss Tropical Public Health Institute, Basel</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Seemann, Torsten" sort="Seemann, Torsten" uniqKey="Seemann T" first="Torsten" last="Seemann">Torsten Seemann</name>
<affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Johnson, Paul D R" sort="Johnson, Paul D R" uniqKey="Johnson P" first="Paul D. R." last="Johnson">Paul D. R. Johnson</name>
<affiliation wicri:level="1"><nlm:aff id="aff9"><addr-line>Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Infectious Diseases, Austin Health, Heidelberg, Victoria</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Davies, John K" sort="Davies, John K" uniqKey="Davies J" first="John K." last="Davies">John K. Davies</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Monash University, Clayton, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology, Monash University, Clayton, Victoria</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jenkin, Grant A" sort="Jenkin, Grant A" uniqKey="Jenkin G" first="Grant A." last="Jenkin">Grant A. Jenkin</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Monash University, Clayton, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology, Monash University, Clayton, Victoria</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pluschke, Gerd" sort="Pluschke, Gerd" uniqKey="Pluschke G" first="Gerd" last="Pluschke">Gerd Pluschke</name>
<affiliation wicri:level="1"><nlm:aff id="aff7"><addr-line>Swiss Tropical Public Health Institute, Basel, Switzerland</addr-line>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Swiss Tropical Public Health Institute, Basel</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stinear, Timothy P" sort="Stinear, Timothy P" uniqKey="Stinear T" first="Timothy P." last="Stinear">Timothy P. Stinear</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Department of Microbiology, Monash University, Clayton, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology, Monash University, Clayton, Victoria</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria</wicri:regionArea>
</affiliation>
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<series><title level="j">PLoS Neglected Tropical Diseases</title>
<idno type="ISSN">1935-2727</idno>
<idno type="eISSN">1935-2735</idno>
<imprint><date when="2010">2010</date>
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<front><div type="abstract" xml:lang="en"><p>A specific and sensitive serodiagnostic test for <italic>Mycobacterium ulcerans</italic>
infection would greatly assist the diagnosis of Buruli ulcer and would also facilitate seroepidemiological surveys. By comparative genomics, we identified 45 potential <italic>M. ulcerans</italic>
specific proteins, of which we were able to express and purify 33 in <italic>E. coli</italic>
. Sera from 30 confirmed Buruli ulcer patients, 24 healthy controls from the same endemic region and 30 healthy controls from a non-endemic region in Benin were screened for antibody responses to these specific proteins by ELISA. Serum IgG responses of Buruli ulcer patients were highly variable, however, seven proteins (MUP045, MUP057, MUL_0513, Hsp65, and the polyketide synthase domains ER, AT propionate, and KR A) showed a significant difference between patient and non-endemic control antibody responses. However, when sera from the healthy control subjects living in the same Buruli ulcer endemic area as the patients were examined, none of the proteins were able to discriminate between these two groups. Nevertheless, six of the seven proteins showed an ability to distinguish people living in an endemic area from those in a non-endemic area with an average sensitivity of 69% and specificity of 88%, suggesting exposure to <italic>M. ulcerans</italic>
. Further validation of these six proteins is now underway to assess their suitability for use in Buruli ulcer seroepidemiological studies. Such studies are urgently needed to assist efforts to uncover environmental reservoirs and understand transmission pathways of the <italic>M. ulcerans</italic>
.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Negl Trop Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS Negl Trop Dis</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosntds</journal-id>
<journal-title-group><journal-title>PLoS Neglected Tropical Diseases</journal-title>
</journal-title-group>
<issn pub-type="ppub">1935-2727</issn>
<issn pub-type="epub">1935-2735</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21072233</article-id>
<article-id pub-id-type="pmc">2970529</article-id>
<article-id pub-id-type="publisher-id">09-PNTD-RA-0749R4</article-id>
<article-id pub-id-type="doi">10.1371/journal.pntd.0000872</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline"><subject>Genetics and Genomics/Comparative Genomics</subject>
<subject>Infectious Diseases/Neglected Tropical Diseases</subject>
<subject>Microbiology/Medical Microbiology</subject>
<subject>Molecular Biology/Bioinformatics</subject>
</subj-group>
</article-categories>
<title-group><article-title>Serological Evaluation of <italic>Mycobacterium ulcerans</italic>
Antigens Identified by Comparative Genomics</article-title>
<alt-title alt-title-type="running-head">Identification of Novel <italic>M. ulcerans</italic>
Antigens</alt-title>
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<contrib-group><contrib contrib-type="author"><name><surname>Pidot</surname>
<given-names>Sacha J.</given-names>
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<xref ref-type="aff" rid="aff1"><sup>1</sup>
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<xref ref-type="aff" rid="aff2"><sup>2</sup>
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</contrib>
<contrib contrib-type="author"><name><surname>Porter</surname>
<given-names>Jessica L.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marsollier</surname>
<given-names>Laurent</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chauty</surname>
<given-names>Annick</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Migot-Nabias</surname>
<given-names>Florence</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Badaut</surname>
<given-names>Cyril</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>5</sup>
</xref>
<xref ref-type="aff" rid="aff6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bénard</surname>
<given-names>Angèle</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ruf</surname>
<given-names>Marie-Therese</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Seemann</surname>
<given-names>Torsten</given-names>
</name>
<xref ref-type="aff" rid="aff8"><sup>8</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Johnson</surname>
<given-names>Paul D. R.</given-names>
</name>
<xref ref-type="aff" rid="aff9"><sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Davies</surname>
<given-names>John K.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jenkin</surname>
<given-names>Grant A.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pluschke</surname>
<given-names>Gerd</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Stinear</surname>
<given-names>Timothy P.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Department of Microbiology, Monash University, Clayton, Victoria, Australia</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia</addr-line>
</aff>
<aff id="aff3"><label>3</label>
<addr-line>Groupe d'Étude des Interactions Hôte-Pathogène, Université d'Angers, Angers, France</addr-line>
</aff>
<aff id="aff4"><label>4</label>
<addr-line>Centre de Dépistage et de Traitement de l'ulcère de Buruli, Pobè, Benin</addr-line>
</aff>
<aff id="aff5"><label>5</label>
<addr-line>Institut de Recherche pour le Développement UMR216, Mère et enfant face aux infections tropicales, Paris, France</addr-line>
</aff>
<aff id="aff6"><label>6</label>
<addr-line>Faculté de Pharmacie, Université Paris Descartes, Paris, France</addr-line>
</aff>
<aff id="aff7"><label>7</label>
<addr-line>Swiss Tropical Public Health Institute, Basel, Switzerland</addr-line>
</aff>
<aff id="aff8"><label>8</label>
<addr-line>Victorian Bioinformatics Consortium, Monash University, Clayton, Victoria, Australia</addr-line>
</aff>
<aff id="aff9"><label>9</label>
<addr-line>Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Phillips</surname>
<given-names>Richard O.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Kwame Nkrumah University of Science and Technology (KNUST) School of Medical Sciences, Ghana</aff>
<author-notes><corresp id="cor1">* E-mail: <email>tstinear@unimelb.edu.au</email>
</corresp>
<fn fn-type="con"><p>Conceived and designed the experiments: SJP JKD GP TPS. Performed the experiments: SJP JLP LM AB MTR. Analyzed the data: SJP LM AB MTR TS PDRJ GAJ GP TPS. Contributed reagents/materials/analysis tools: SJP JLP LM AC FMN CB AB MTR TS PDRJ GAJ GP. Wrote the paper: SJP AB GAJ TPS.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><month>11</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub"><day>2</day>
<month>11</month>
<year>2010</year>
</pub-date>
<volume>4</volume>
<issue>11</issue>
<elocation-id>e872</elocation-id>
<history><date date-type="received"><day>22</day>
<month>12</month>
<year>2009</year>
</date>
<date date-type="accepted"><day>6</day>
<month>10</month>
<year>2010</year>
</date>
</history>
<permissions><copyright-statement>Pidot et al.</copyright-statement>
<copyright-year>2010</copyright-year>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p>
</license>
</permissions>
<abstract><p>A specific and sensitive serodiagnostic test for <italic>Mycobacterium ulcerans</italic>
infection would greatly assist the diagnosis of Buruli ulcer and would also facilitate seroepidemiological surveys. By comparative genomics, we identified 45 potential <italic>M. ulcerans</italic>
specific proteins, of which we were able to express and purify 33 in <italic>E. coli</italic>
. Sera from 30 confirmed Buruli ulcer patients, 24 healthy controls from the same endemic region and 30 healthy controls from a non-endemic region in Benin were screened for antibody responses to these specific proteins by ELISA. Serum IgG responses of Buruli ulcer patients were highly variable, however, seven proteins (MUP045, MUP057, MUL_0513, Hsp65, and the polyketide synthase domains ER, AT propionate, and KR A) showed a significant difference between patient and non-endemic control antibody responses. However, when sera from the healthy control subjects living in the same Buruli ulcer endemic area as the patients were examined, none of the proteins were able to discriminate between these two groups. Nevertheless, six of the seven proteins showed an ability to distinguish people living in an endemic area from those in a non-endemic area with an average sensitivity of 69% and specificity of 88%, suggesting exposure to <italic>M. ulcerans</italic>
. Further validation of these six proteins is now underway to assess their suitability for use in Buruli ulcer seroepidemiological studies. Such studies are urgently needed to assist efforts to uncover environmental reservoirs and understand transmission pathways of the <italic>M. ulcerans</italic>
.</p>
</abstract>
<abstract abstract-type="summary"><title>Author Summary</title>
<p>Buruli ulcer is a slowly progressive but potentially devastating disease of skin and subcutaneous tissue caused by the bacterium <italic>Mycobacterium ulcerans.</italic>
The disease is widespread throughout West and Central Africa, and some countries in the region have established Buruli ulcer control programs. Buruli ulcer is difficult to distinguish from other chronic skin conditions that require different treatments, and there is an urgent need for an accurate point-of-care diagnostic test. In this study, we have used genomic techniques to identify 45 potential <italic>M. ulcerans</italic>
–specific antigens, 33 of which we have been able to produce and purify. We tested these proteins against sera from patients, healthy people living in the same region as the patients and from individuals living in a region with no cases of Buruli ulcer. We found that seven proteins were able to elicit antibody responses that were significantly different between patients and the control subjects from the non-endemic region but not from the healthy individuals in the same Buruli ulcer endemic region. Further analysis showed that six of these <italic>M. ulcerans</italic>
proteins might be useful as markers of exposure to <italic>M. ulcerans</italic>
and could be developed into tools to uncover environmental reservoirs and understand transmission pathways of the bacterium.</p>
</abstract>
<counts><page-count count="10"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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