{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:27:04Z","timestamp":1790882824802,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,6,7]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>Brugia malayi<\/jats:italic>\n                    , 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\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    , 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 \u201chypothetical,\u201d 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\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    as well.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1011481108","type":"journal-article","created":{"date-parts":[[2011,5,24]],"date-time":"2011-05-24T00:31:06Z","timestamp":1306197066000},"page":"9649-9654","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":94,"title":["Stage-specific proteomic expression patterns of the human filarial parasite\n                    <i>Brugia malayi<\/i>\n                    and its endosymbiont\n                    <i>Wolbachia<\/i>"],"prefix":"10.1073","volume":"108","author":[{"given":"Sasisekhar","family":"Bennuru","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojing","family":"Meng","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC\u2013Frederick, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M. C.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshanak Tolouei","family":"Semnani","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Ghedin","sequence":"additional","affiliation":[{"name":"Center for Vaccine Research, Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"King","family":"Chan","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC\u2013Frederick, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC\u2013Frederick, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Veenstra","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC\u2013Frederick, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Nutman","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,5,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"e410","DOI":"10.1371\/journal.pntd.0000410","article-title":"Brugia malayi excreted\/secreted proteins at the host\/parasite interface: Stage- and gender-specific proteomic profiling","volume":"3","author":"Bennuru S","year":"2009","unstructured":"S Bennuru, et al., Brugia malayi excreted\/secreted proteins at the host\/parasite interface: Stage- and gender-specific proteomic profiling. PLoS Negl Trop Dis 3, e410 (2009).","journal-title":"PLoS Negl Trop Dis"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molbiopara.2008.02.007","article-title":"The secretome of the filarial parasite, Brugia malayi: Proteomic profile of adult excretory-secretory products","volume":"160","author":"Hewitson JP","year":"2008","unstructured":"JP Hewitson, et al., The secretome of the filarial parasite, Brugia malayi: Proteomic profile of adult excretory-secretory products. Mol Biochem Parasitol 160, 8\u201321 (2008).","journal-title":"Mol Biochem Parasitol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"e326","DOI":"10.1371\/journal.pntd.0000326","article-title":"Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products","volume":"2","author":"Moreno Y","year":"2008","unstructured":"Y Moreno, TG Geary, Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products. PLoS Negl Trop Dis 2, e326 (2008).","journal-title":"PLoS Negl Trop Dis"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1126\/science.1145406","article-title":"Draft genome of the filarial nematode parasite Brugia malayi","volume":"317","author":"Ghedin E","year":"2007","unstructured":"E Ghedin, et al., Draft genome of the filarial nematode parasite Brugia malayi. Science 317, 1756\u20131760 (2007).","journal-title":"Science"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/cfg.66","article-title":"Conserved \u2018hypothetical\u2019 proteins: New hints and new puzzles","volume":"2","author":"Galperin MY","year":"2001","unstructured":"MY Galperin, Conserved \u2018hypothetical\u2019 proteins: New hints and new puzzles. Comp Funct Genomics 2, 14\u201318 (2001).","journal-title":"Comp Funct Genomics"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1093\/nar\/gki615","article-title":"Protein length in eukaryotic and prokaryotic proteomes","volume":"33","author":"Brocchieri L","year":"2005","unstructured":"L Brocchieri, S Karlin, Protein length in eukaryotic and prokaryotic proteomes. Nucleic Acids Res 33, 3390\u20133400 (2005).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"8390","DOI":"10.1073\/pnas.0307270101","article-title":"Global analysis of predicted proteomes: Functional adaptation of physical properties","volume":"101","author":"Knight CG","year":"2004","unstructured":"CG Knight, R Kassen, H Hebestreit, PB Rainey, Global analysis of predicted proteomes: Functional adaptation of physical properties. 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