{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:09:05Z","timestamp":1776424145155,"version":"3.51.2"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"National Science Foundation China","award":["81501772"],"award-info":[{"award-number":["81501772"]}]},{"name":"National Science Foundation China","award":["81171611"],"award-info":[{"award-number":["81171611"]}]},{"name":"NIH","award":["AI080615"],"award-info":[{"award-number":["AI080615"]}]},{"name":"NIH","award":["AI116620"],"award-info":[{"award-number":["AI116620"]}]},{"name":"NIH","award":["AI083640"],"award-info":[{"award-number":["AI083640"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            High-temperature requirement protease A (HtrA) represents a family of serine proteases that play important roles in microbial biology. Unlike the genomes of most organisms, that of\n            <jats:named-content content-type=\"genus-species\">Borrelia burgdorferi<\/jats:named-content>\n            notably encodes a single HtrA gene product, termed BbHtrA. Previous studies identified a few substrates of BbHtrA; however, their physiological relevance could not be ascertained, as targeted deletion of the gene has not been successful. Here we show that Bb\n            <jats:italic>htrA<\/jats:italic>\n            transcripts are induced during spirochete growth either in the stationary phase or at elevated temperature. Successful generation of a Bb\n            <jats:italic>htrA<\/jats:italic>\n            deletion mutant and restoration by genetic complementation suggest a nonessential role for this protease in microbial viability; however, its remarkable growth, morphological, and structural defects during cultivation at 37\u00b0C confirm a high-temperature requirement for protease activation and function. The Bb\n            <jats:italic>htrA<\/jats:italic>\n            -deficient spirochetes were unable to establish infection of mice, as evidenced by assessment of culture, PCR, and serology. We show that transcript abundance as well as proteolytic processing of a borrelial protein required for cell fission and infectivity, BB0323, is impaired in Bb\n            <jats:italic>htrA<\/jats:italic>\n            mutants grown at 37\u00b0C, which likely contributed to their inability to survive in a mammalian host. Together, these results demonstrate the physiological relevance of a unique temperature-regulated borrelial protease, BbHtrA, which further enlightens our knowledge of intriguing aspects of spirochete biology and infectivity.\n          <\/jats:p>","DOI":"10.1128\/iai.00360-16","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T03:13:47Z","timestamp":1465269227000},"page":"2372-2381","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts"],"prefix":"10.1128","volume":"84","author":[{"given":"Meiping","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"},{"name":"College of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavita","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghna","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozlem","family":"Buyuktanir","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Veterinary Medicine, Ondokuz Mayis University, Samsun, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuwu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamoltip","family":"Promnares","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongliang","family":"Lou","sequence":"additional","affiliation":[{"name":"College of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"X. 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