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Genome sequencing of two species of relapsing fever spirochaetes, <jats:italic>Borrelia hermsii<\/jats:italic> and <jats:italic>Borrelia turicatae,<\/jats:italic> identified a chromosomal open reading frame, designated <jats:italic>bhpA<\/jats:italic>, not present in the Lyme disease spirochaete <jats:italic>Borrelia burgdorferi<\/jats:italic>. The predicted amino acid sequence of <jats:italic>bhpA<\/jats:italic> was homologous with the HtrA serine proteases, which are involved with stress responses and virulence in other bacteria. <jats:italic>B.\u2003hermsii<\/jats:italic> produced an active serine protease that was recognized by BhpA antibodies and the recombinant BhpA protein\u2010degraded \u03b2\u2010casein. <jats:italic>bhpA<\/jats:italic> was transcribed <jats:italic>in vitro<\/jats:italic> at all growth temperatures and transcription levels were slightly elevated at higher temperatures. These results correlated with the synthesis of BhpA during <jats:italic>B.\u2003hermsii<\/jats:italic> infection in mice. With the exception of <jats:italic>Borrelia recurrentis<\/jats:italic>, the <jats:italic>bhpA<\/jats:italic> gene, protein and enzymatic activity were found in all relapsing fever spirochaetes, but not in Lyme disease or related spirochaetes. Heterologous expression of <jats:italic>bhpA<\/jats:italic> in <jats:italic>B.\u2003burgdorferi<\/jats:italic> increased the spirochaete's resistance to both oxidative stress and killing by human neutrophils. Therefore, we propose that <jats:italic>bhpA<\/jats:italic> encodes a unique and functional serine protease in relapsing fever spirochaetes. This periplasmic enzyme may prevent the accumulation of proteins damaged by the innate immune response and contribute to the ability of the relapsing fever spirochaetes to achieve high cell densities in blood.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2006.05122.x","type":"journal-article","created":{"date-parts":[[2006,3,8]],"date-time":"2006-03-08T18:38:15Z","timestamp":1141843095000},"page":"710-722","source":"Crossref","is-referenced-by-count":14,"title":["Relapsing fever spirochaetes produce a serine protease that provides resistance to oxidative stress and killing by neutrophils"],"prefix":"10.1111","volume":"60","author":[{"given":"Cyril","family":"Guyard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Battisti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra J.","family":"Raffel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merry E.","family":"Schrumpf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline R.","family":"Whitney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan G.","family":"Krum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Porcella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank R.","family":"DeLeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom G.","family":"Schwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,3,8]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"521","article-title":"Isolation and cultivation of Lyme disease spirochetes","volume":"57","author":"Barbour A.G.","year":"1984","journal-title":"Yale J Biol Med"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.2.511-523.1996"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.6.3371-3383.2003"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/516276"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.5.3389-3397.2001"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(92)90117-7"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207271"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00658-5"},{"key":"e_1_2_6_10_1","first-page":"41","volume-title":"A Symposium on Relapsing Fever in the Americas.","author":"Davis G.E.","year":"1942"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.12.7357-7359.2004"},{"key":"e_1_2_6_12_1","volume-title":"Borrelia. 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