Histidine Kinase-Mediated Production and Autoassembly of <i>Porphyromonas gingivalis</i> Fimbriae

<jats:title>ABSTRACT</jats:title> <jats:p> <jats:italic>Porphyromonas gingivalis</jats:italic> , a Gram-negative oral anaerobe, is strongly associated with chronic adult periodontitis, and it utilizes FimA fimbriae to persistently colonize and evade host defenses in the periodontal crevice. The FimA-related gene cluster (the <jats:italic>fim</jats:italic> gene cluster) is positively regulated by the FimS-FimR two-component system. In this study, comparative analyses between fimbriate type strain ATCC 33277 and fimbria-deficient strain W83 revealed differences in their <jats:italic>fimS</jats:italic> loci, which encode FimS histidine kinase. Using a reciprocal gene exchange system, we established that FimS from W83 is malfunctional. Complementation analysis with chimeric <jats:italic>fimS</jats:italic> constructs revealed that W83 FimS has a defective kinase domain due to a truncated conserved G3 box motif that provides an ATP-binding pocket. The introduction of the functional <jats:italic>fimS</jats:italic> from 33277 restored the production, but not polymerization, of endogenous FimA subunits in W83. Further analyses with a <jats:italic>fimA</jats:italic> -exchanged W83 isogenic strain showed that even the fimbria-deficient W83 retains the ability to polymerize FimA from 33277, indicating the assembly of mature FimA by a primary structure-dependent mechanism. It also was shown that the substantial expression of 33277-type FimA fimbriae in the W83 derivative requires the introduction and expression of the functional 33277 <jats:italic>fimS</jats:italic> . These findings indicate that FimSR is the unique and universal regulatory system that activates the <jats:italic>fim</jats:italic> gene cluster in a <jats:italic>fimA</jats:italic> genotype-independent manner. </jats:p>