{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T01:33:09Z","timestamp":1772501589446,"version":"3.50.1"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The Lyme disease spirochete\n            <jats:named-content content-type=\"genus-species\">Borrelia burgdorferi<\/jats:named-content>\n            senses and responds to environmental cues as it transits between the tick vector and vertebrate host. Failure to properly adapt can block transmission of the spirochete and persistence in either vector or host. We previously identified BBD18, a novel plasmid-encoded protein of\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            , as a putative repressor of the host-essential factor OspC. In this study, we investigate the\n            <jats:italic>in vivo<\/jats:italic>\n            role of BBD18 as a regulatory protein, using an experimental mouse-tick model system that closely resembles the natural infectious cycle of\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            . We show that spirochetes that have been engineered to constitutively produce BBD18 can colonize and persist in ticks but do not infect mice when introduced by either tick bite or needle inoculation. Conversely, spirochetes lacking BBD18 can persistently infect mice but are not acquired by feeding ticks. Through site-directed mutagenesis, we have demonstrated that abrogation of spirochete infection in mice by overexpression of BBD18 occurs only with\n            <jats:italic>bbd18<\/jats:italic>\n            alleles that can suppress OspC synthesis. Finally, we demonstrate that BBD18-mediated regulation does not utilize a previously described\n            <jats:italic>ospC<\/jats:italic>\n            operator sequence required by\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            for persistence in immunocompetent mice. These data lead us to conclude that BBD18 does not represent the putative repressor utilized by\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            for the specific downregulation of OspC in the mammalian host. Rather, we suggest that BBD18 exhibits features more consistent with those of a global regulatory protein whose critical role occurs during spirochete acquisition by feeding ticks.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Lyme disease, caused by\n            <jats:named-content content-type=\"genus-species\">Borrelia burgdorferi<\/jats:named-content>\n            , is the most common arthropod-borne disease in North America.\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            is transmitted to humans and other vertebrate hosts by ticks as they take a blood meal. Transmission between vectors and hosts requires the bacterium to sense changes in the environment and adapt. However, the mechanisms involved in this process are not well understood. By determining how\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            cycles between two very different environments, we can potentially establish novel ways to interfere with transmission and limit infection of this vector-borne pathogen. We are studying a regulatory protein called BBD18 that we recently described. We found that too much BBD18 interferes with the spirochete\u2019s ability to establish infection in mice, whereas too little BBD18 appears to prevent colonization in ticks. Our study provides new insight into key elements of the infectious cycle of the Lyme disease spirochete.\n          <\/jats:p>","DOI":"10.1128\/mbio.01017-14","type":"journal-article","created":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T03:50:10Z","timestamp":1396410610000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Regulatory Protein BBD18 of the Lyme Disease Spirochete: Essential Role During Tick Acquisition?"],"prefix":"10.1128","volume":"5","author":[{"given":"Beth M.","family":"Hayes","sequence":"first","affiliation":[{"name":"Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel P.","family":"Dulebohn","sequence":"additional","affiliation":[{"name":"Laboratory of Zoonotic Pathogens, Rocky Mountain 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