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Very little is known about how PF are assembled within the periplasm of spirochaetal cells. Herein, we report that FliD (BB0149), a flagellar cap protein (also named hook\u2010associated protein 2), controls flagellin stability and flagellar filament assembly in the Lyme disease spirochete <jats:italic>Borrelia burgdorferi<\/jats:italic>. Deletion of <jats:italic>fliD<\/jats:italic> leads to non\u2010motile mutant cells that are unable to assemble flagellar filaments and pentagon\u2010shaped caps (10\u00a0nm in diameter, 12\u00a0nm in length). Interestingly, FlaB, a major flagellin protein of <jats:italic>B. burgdorferi<\/jats:italic>, is degraded in the <jats:italic>fliD<\/jats:italic> mutant but not in other flagella\u2010deficient mutants (i.e., in the hook, rod, or MS\u2010ring). Biochemical and genetic studies reveal that HtrA, a serine protease of <jats:italic>B. burgdorferi<\/jats:italic>, controls FlaB turnover. Specifically, HtrA degrades unfolded but not polymerized FlaB, and deletion of <jats:italic>htrA<\/jats:italic> increases the level of FlaB in the <jats:italic>fliD<\/jats:italic> mutant. Collectively, we propose that the flagellar cap protein FliD promotes flagellin polymerization and filament growth in the periplasm. Deletion of <jats:italic>fliD<\/jats:italic> abolishes this process, which leads to leakage of unfolded FlaB proteins into the periplasm where they are degraded by HtrA, a protease that prevents accumulation of toxic products in the periplasm.<\/jats:p>","DOI":"10.1111\/mmi.14243","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T00:52:49Z","timestamp":1552956769000},"page":"1652-1670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Analysis of a flagellar filament cap mutant reveals that HtrA serine protease degrades unfolded flagellin protein in the periplasm of <i>Borrelia burgdorferi<\/i>"],"prefix":"10.1111","volume":"111","author":[{"given":"Kai","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oral and Craniofacial Molecular Biology Philips Research Institute, Virginia Commonwealth University Richmond VI 23298 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