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Disease pathogenesis is induced by inflammatory responses following the death of the parasite. <jats:italic>Wolbachia<\/jats:italic> endosymbionts of filariae are potent inducers of innate and adaptive inflammation and bacterial lipoproteins have been identified as the ligands that bind toll-like receptors (TLR) 2 and TLR6. Lipoproteins are important structural and functional components of bacteria and therefore enzymes involved in <jats:italic>Wolbachia<\/jats:italic> lipoprotein biosynthesis are potential chemotherapeutic targets.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Globomycin, a signal peptidase II (LspA) inhibitor, has activity against Gram-negative bacteria and a putative <jats:italic>lspA<\/jats:italic> gene has been identified from the <jats:italic>Wolbachia<\/jats:italic> genome of <jats:italic>Brugia malayi<\/jats:italic> (<jats:italic>w<\/jats:italic> Bm). The amino acids required for function are strictly conserved and functionality was verified by complementation tests in a temperature-sensitive <jats:italic>Escherichia coli lspA<\/jats:italic> mutant. Also, transformation of wild type <jats:italic>E. coli<\/jats:italic> with <jats:italic>Wolbachia lspA<\/jats:italic> conferred significant globomycin resistance. A cell-based screen has been developed utilizing a <jats:italic>Wolbachia<\/jats:italic>-containing <jats:italic>Aedes albopictus<\/jats:italic> cell line to assay novel compounds active against <jats:italic>Wolbachia<\/jats:italic>. Globomycin was screened using this assay, which resulted in a dose-dependent reduction in <jats:italic>Wolbachia<\/jats:italic> load. Furthermore, globomycin was also effective in reducing the motility and viability of adult <jats:italic>B. malayi in vitro<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These studies validate lipoprotein biosynthesis as a target in an organism for which no genetic tools are available. Further studies to evaluate drugs targeting this pathway are underway as part of the A-WOL drug discovery and development program.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1756-3305-3-99","type":"journal-article","created":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T18:15:15Z","timestamp":1287166515000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Lipoprotein biosynthesis as a target for anti-Wolbachia treatment of filarial nematodes"],"prefix":"10.1186","volume":"3","author":[{"given":"Kelly L","family":"Johnston","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Ford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barton E","family":"Slatko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,10,14]]},"reference":[{"key":"227_CR1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0065-308X(05)60004-8","volume":"60","author":"MJ Taylor","year":"2005","unstructured":"Taylor MJ, Bandi C, Hoerauf A: Wolbachia bacterial endosymbionts of filarial nematodes. 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