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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Stage-specific proteomic expression patterns of the human filarial parasite <italic>Brugia malayi</italic>
and its endosymbiont <italic>Wolbachia</italic>
</title>
<author><name sortKey="Bennuru, Sasisekhar" sort="Bennuru, Sasisekhar" uniqKey="Bennuru S" first="Sasisekhar" last="Bennuru">Sasisekhar Bennuru</name>
<affiliation><nlm:aff id="aff1">Laboratory of Parasitic Diseases,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Meng, Zhaojing" sort="Meng, Zhaojing" uniqKey="Meng Z" first="Zhaojing" last="Meng">Zhaojing Meng</name>
<affiliation><nlm:aff id="aff2">Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ribeiro, Jose M C" sort="Ribeiro, Jose M C" uniqKey="Ribeiro J" first="José M. C." last="Ribeiro">José M. C. Ribeiro</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff3">Laboratory of Malaria and Vector Research,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Semnani, Roshanak Tolouei" sort="Semnani, Roshanak Tolouei" uniqKey="Semnani R" first="Roshanak Tolouei" last="Semnani">Roshanak Tolouei Semnani</name>
<affiliation><nlm:aff id="aff1">Laboratory of Parasitic Diseases,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ghedin, Elodie" sort="Ghedin, Elodie" uniqKey="Ghedin E" first="Elodie" last="Ghedin">Elodie Ghedin</name>
<affiliation><nlm:aff id="aff4">Center for Vaccine Research, Department of Computational and Systems Biology,<institution>University of Pittsburgh School of Medicine</institution>
, Pittsburgh, PA 15261</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, King" sort="Chan, King" uniqKey="Chan K" first="King" last="Chan">King Chan</name>
<affiliation><nlm:aff id="aff2">Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lucas, David A" sort="Lucas, David A" uniqKey="Lucas D" first="David A." last="Lucas">David A. Lucas</name>
<affiliation><nlm:aff id="aff2">Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Veenstra, Timothy D" sort="Veenstra, Timothy D" uniqKey="Veenstra T" first="Timothy D." last="Veenstra">Timothy D. Veenstra</name>
<affiliation><nlm:aff id="aff2">Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name>
<affiliation><nlm:aff id="aff1">Laboratory of Parasitic Diseases,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892;</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">21606368</idno>
<idno type="pmc">3111283</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111283</idno>
<idno type="RBID">PMC:3111283</idno>
<idno type="doi">10.1073/pnas.1011481108</idno>
<date when="2011">2011</date>
<idno type="wicri:Area/Pmc/Corpus">003165</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003165</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Stage-specific proteomic expression patterns of the human filarial parasite <italic>Brugia malayi</italic>
and its endosymbiont <italic>Wolbachia</italic>
</title>
<author><name sortKey="Bennuru, Sasisekhar" sort="Bennuru, Sasisekhar" uniqKey="Bennuru S" first="Sasisekhar" last="Bennuru">Sasisekhar Bennuru</name>
<affiliation><nlm:aff id="aff1">Laboratory of Parasitic Diseases,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Meng, Zhaojing" sort="Meng, Zhaojing" uniqKey="Meng Z" first="Zhaojing" last="Meng">Zhaojing Meng</name>
<affiliation><nlm:aff id="aff2">Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ribeiro, Jose M C" sort="Ribeiro, Jose M C" uniqKey="Ribeiro J" first="José M. C." last="Ribeiro">José M. C. Ribeiro</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff3">Laboratory of Malaria and Vector Research,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Semnani, Roshanak Tolouei" sort="Semnani, Roshanak Tolouei" uniqKey="Semnani R" first="Roshanak Tolouei" last="Semnani">Roshanak Tolouei Semnani</name>
<affiliation><nlm:aff id="aff1">Laboratory of Parasitic Diseases,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ghedin, Elodie" sort="Ghedin, Elodie" uniqKey="Ghedin E" first="Elodie" last="Ghedin">Elodie Ghedin</name>
<affiliation><nlm:aff id="aff4">Center for Vaccine Research, Department of Computational and Systems Biology,<institution>University of Pittsburgh School of Medicine</institution>
, Pittsburgh, PA 15261</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chan, King" sort="Chan, King" uniqKey="Chan K" first="King" last="Chan">King Chan</name>
<affiliation><nlm:aff id="aff2">Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lucas, David A" sort="Lucas, David A" uniqKey="Lucas D" first="David A." last="Lucas">David A. Lucas</name>
<affiliation><nlm:aff id="aff2">Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Veenstra, Timothy D" sort="Veenstra, Timothy D" uniqKey="Veenstra T" first="Timothy D." last="Veenstra">Timothy D. Veenstra</name>
<affiliation><nlm:aff id="aff2">Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name>
<affiliation><nlm:aff id="aff1">Laboratory of Parasitic Diseases,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892;</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Global proteomic analyses of pathogens have thus far been limited to unicellular organisms (e.g., protozoa and bacteria). Proteomic analyses of most eukaryotic pathogens (e.g., helminths) have been restricted to specific organs, specific stages, or secretomes. We report here a large-scale proteomic characterization of almost all the major mammalian stages of <italic>Brugia malayi</italic>
, a causative agent of lymphatic filariasis, resulting in the identification of more than 62% of the products predicted from the Bm draft genome. The analysis also yielded much of the proteome of <italic>Wolbachia</italic>
, the obligate endosymbiont of Bm that also expressed proteins in a stage-specific manner. Of the 11,610 predicted Bm gene products, 7,103 were definitively identified from adult male, adult female, blood-borne and uterine microfilariae, and infective L3 larvae. Among the 4,956 gene products (42.5%) inferred from the genome as “hypothetical,” the present study was able to confirm 2,336 (47.1%) as bona fide proteins. Analysis of protein families and domains coupled with stage-specific expression highlight the important pathways that benefit the parasite during its development in the host. Gene set enrichment analysis identified extracellular matrix proteins and those with immunologic effects as enriched in the microfilarial and L3 stages. Parasite sex- and stage-specific protein expression identified those pathways related to parasite differentiation and demonstrates stage-specific expression by the Bm endosymbiont <italic>Wolbachia</italic>
as well.</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">Proc Natl Acad Sci U S A</journal-id>
<journal-id journal-id-type="hwp">pnas</journal-id>
<journal-id journal-id-type="pmc">pnas</journal-id>
<journal-id journal-id-type="publisher-id">PNAS</journal-id>
<journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title>
</journal-title-group>
<issn pub-type="ppub">0027-8424</issn>
<issn pub-type="epub">1091-6490</issn>
<publisher><publisher-name>National Academy of Sciences</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21606368</article-id>
<article-id pub-id-type="pmc">3111283</article-id>
<article-id pub-id-type="publisher-id">201011481</article-id>
<article-id pub-id-type="doi">10.1073/pnas.1011481108</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject>
<subj-group><subject>Microbiology</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Stage-specific proteomic expression patterns of the human filarial parasite <italic>Brugia malayi</italic>
and its endosymbiont <italic>Wolbachia</italic>
</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Bennuru</surname>
<given-names>Sasisekhar</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Meng</surname>
<given-names>Zhaojing</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ribeiro</surname>
<given-names>José M. C.</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Semnani</surname>
<given-names>Roshanak Tolouei</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ghedin</surname>
<given-names>Elodie</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chan</surname>
<given-names>King</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lucas</surname>
<given-names>David A.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Veenstra</surname>
<given-names>Timothy D.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nutman</surname>
<given-names>Thomas B.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<aff id="aff1"><sup>a</sup>
Laboratory of Parasitic Diseases,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892;</aff>
<aff id="aff2"><sup>b</sup>
Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC–Frederick, Frederick, MD 21702;</aff>
<aff id="aff3"><sup>c</sup>
Laboratory of Malaria and Vector Research,<institution>National Institute of Allergy and Infectious Diseases</institution>
, Bethesda, MD 20892; and</aff>
<aff id="aff4"><sup>d</sup>
Center for Vaccine Research, Department of Computational and Systems Biology,<institution>University of Pittsburgh School of Medicine</institution>
, Pittsburgh, PA 15261</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>1</sup>
To whom correspondence should be addressed. E-mail: <email>bennurus@niaid.nih.gov</email>
.</corresp>
<fn fn-type="edited-by"><p>Edited by Paul B. Rainey, Massey University, Auckland, New Zealand, and accepted by the Editorial Board May 1, 2011 (received for review August 5, 2010)</p>
</fn>
<fn fn-type="con"><p>Author contributions: S.B. and T.B.N. designed research; S.B., Z.M., J.M.C.R., K.C., and D.A.L. performed research; J.M.C.R., E.G., T.D.V., and T.B.N. contributed new reagents/analytic tools; S.B., Z.M., J.M.C.R., R.T.S., E.G., T.D.V., and T.B.N. analyzed data; and S.B. and T.B.N. wrote the paper.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>7</day>
<month>6</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>23</day>
<month>5</month>
<year>2011</year>
</pub-date>
<volume>108</volume>
<issue>23</issue>
<fpage>9649</fpage>
<lpage>9654</lpage>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.201011481.pdf"></self-uri>
<abstract><p>Global proteomic analyses of pathogens have thus far been limited to unicellular organisms (e.g., protozoa and bacteria). Proteomic analyses of most eukaryotic pathogens (e.g., helminths) have been restricted to specific organs, specific stages, or secretomes. We report here a large-scale proteomic characterization of almost all the major mammalian stages of <italic>Brugia malayi</italic>
, a causative agent of lymphatic filariasis, resulting in the identification of more than 62% of the products predicted from the Bm draft genome. The analysis also yielded much of the proteome of <italic>Wolbachia</italic>
, the obligate endosymbiont of Bm that also expressed proteins in a stage-specific manner. Of the 11,610 predicted Bm gene products, 7,103 were definitively identified from adult male, adult female, blood-borne and uterine microfilariae, and infective L3 larvae. Among the 4,956 gene products (42.5%) inferred from the genome as “hypothetical,” the present study was able to confirm 2,336 (47.1%) as bona fide proteins. Analysis of protein families and domains coupled with stage-specific expression highlight the important pathways that benefit the parasite during its development in the host. Gene set enrichment analysis identified extracellular matrix proteins and those with immunologic effects as enriched in the microfilarial and L3 stages. Parasite sex- and stage-specific protein expression identified those pathways related to parasite differentiation and demonstrates stage-specific expression by the Bm endosymbiont <italic>Wolbachia</italic>
as well.</p>
</abstract>
<kwd-group><kwd>filaria</kwd>
<kwd>nematode</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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