{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:00:05Z","timestamp":1782781205145,"version":"3.54.5"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T00:00:00Z","timestamp":1461024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T00:00:00Z","timestamp":1462320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,5,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In many bacteria, the FtsH protease and its modulators, HflK and HflC, form a large protein complex that contributes to both membrane protein quality control and regulation of the cellular response to environmental stress. Both activities are crucial to the Lyme disease pathogen\n            <jats:named-content content-type=\"genus-species\">Borrelia burgdorferi<\/jats:named-content>\n            , which depends on membrane functions, such as motility, protein transport, and cell signaling, to respond to rapid changes in its environment. Using an inducible system, we demonstrate that FtsH production is essential for both mouse and tick infectivity and for\n            <jats:italic>in vitro<\/jats:italic>\n            growth of\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            . FtsH depletion in\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            cells resulted in membrane deformation and cell death. Overproduction of the protease did not have any detectable adverse effects on\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            growth\n            <jats:italic>in vitro<\/jats:italic>\n            , suggesting that excess FtsH does not proteolytically overwhelm its substrates. In contrast, we did not observe any phenotype for cells lacking the protease modulators HflK and HflC (\u0394HflK\/C), although we examined morphology, growth rate, growth under stress conditions, and the complete mouse-tick infectious cycle. Our results demonstrate that FtsH provides an essential function in the life cycle of the obligate pathogen\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            but that HflK and HflC do not detectably affect FtsH function.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Lyme disease is caused by\n            <jats:named-content content-type=\"genus-species\">Borrelia burgdorferi<\/jats:named-content>\n            , which is maintained in nature in an infectious cycle alternating between small mammals and\n            <jats:italic>Ixodes<\/jats:italic>\n            ticks.\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            produces specific membrane proteins to successfully infect and persist in these diverse organisms. We hypothesized that\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            has a specific mechanism to ensure that membrane proteins are properly folded and biologically active when needed and removed if improperly folded or dysfunctional. Our experiments demonstrate that FtsH, a protease that fulfills this role in other microorganisms, is essential to\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            viability. Cells depleted of FtsH do not survive in laboratory culture medium and cannot colonize mice or ticks, revealing an absolute requirement for this protease. However, the loss of two potential modulators of FtsH activity, HflK and HflC, does not detectably affect\n            <jats:named-content content-type=\"genus-species\">B. burgdorferi<\/jats:named-content>\n            physiology. Our results provide the groundwork for the identification of FtsH substrates that are critical for the bacterium\u2019s viability.\n          <\/jats:p>","DOI":"10.1128\/mbio.00404-16","type":"journal-article","created":{"date-parts":[[2016,4,20]],"date-time":"2016-04-20T01:13:21Z","timestamp":1461114801000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Function of the Borrelia burgdorferi FtsH Homolog Is Essential for Viability both\n            <i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            and Independent of HflK\/C"],"prefix":"10.1128","volume":"7","author":[{"given":"Chen-Yi","family":"Chu","sequence":"first","affiliation":[{"name":"Laboratory of Zoonotic Pathogens, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip 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