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The <jats:italic>cdr<\/jats:italic> gene encodes a coenzyme A disulphide reductase (CoADR) that reduces CoA\u2010disulphides to CoA in an NADH\u2010dependent manner. Based on the abundance of CoA in <jats:italic>B.\u2003burgdorferi<\/jats:italic> and the biochemistry of the enzyme, CoADR has been proposed to play a role in the spirochaete's response to reactive oxygen species. To better understand the physiologic function(s) of <jats:italic>Bb<\/jats:italic>CoADR, we generated a <jats:italic>B.\u2003burgdorferi<\/jats:italic> mutant in which the <jats:italic>cdr<\/jats:italic> gene was disrupted. RT\u2010PCR and 5\u2032\u2010RACE analysis revealed that <jats:italic>cdr<\/jats:italic> and <jats:italic>bb0729<\/jats:italic> are co\u2010transcribed from a single transcriptional start site upstream of the <jats:italic>bb0729<\/jats:italic> coding sequence; a shuttle vector containing the <jats:italic>bb0729\u2010cdr<\/jats:italic> operon and upstream promoter element was used to complement the <jats:italic>cdr<\/jats:italic> mutant. Although the mutant was no more sensitive to hydrogen peroxide than its parent, it did exhibit increased sensitivity to high concentrations of <jats:italic>t<\/jats:italic>\u2010butyl\u2010hydroperoxide, an oxidizing compound that damages spirochetal membranes. Characterization of the mutant during standard (15% oxygen, 6% CO<jats:sub>2<\/jats:sub>) and anaerobic (&lt;\u20031% O<jats:sub>2<\/jats:sub>, 9\u201313% CO<jats:sub>2<\/jats:sub>) cultivation at 37\u00b0C revealed a growth defect under both conditions that was particularly striking during anaerobiosis. The mutant was avirulent by needle inoculation and showed decreased survival in feeding nymphs, but displayed no survival defect in unfed flat nymphs. Based on these results, we propose that <jats:italic>Bb<\/jats:italic>CoADR is necessary to maintain optimal redox ratios for CoA\/CoA\u2010disulphide and NAD<jats:sup>+<\/jats:sup>\/NADH during periods of rapid replication throughout the enzootic cycle, to support thiol\u2010disulphide homeostasis, and to indirectly protect the spirochaete against peroxide\u2010mediated membrane damage; one or more of these functions are essential for infection of the mammalian host by <jats:italic>B.\u2003burgdorferi<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2011.07845.x","type":"journal-article","created":{"date-parts":[[2011,9,16]],"date-time":"2011-09-16T22:38:39Z","timestamp":1316212719000},"page":"679-697","source":"Crossref","is-referenced-by-count":40,"title":["The coenzyme A disulphide reductase of <i>Borrelia burgdorferi<\/i> is important for rapid growth throughout the enzootic cycle and essential for infection of the mammalian host"],"prefix":"10.1111","volume":"82","author":[{"given":"Christian H.","family":"Eggers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Caimano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Malizia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kariu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Cusack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Desrosiers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten R. 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