Transposase-Associated Variation near tnaA in Porphyromonas gingivalis Is Linked to Indole Production and Virulence-Associated Gene Expression.

Indole, a volatile metabolite produced by bacterial tryptophanase (encoded by tnaA) during tryptophan metabolism, contributes to oral malodor and may influence the progression of periodontitis. However, the genetic features underlying strain-specific indole production and its association with bacterial virulence remain unclear. Analysis of a previously published periodontitis cohort revealed that periodontitis severity was associated with salivary indole-related metabolic signatures, which were positively correlated with the abundance of Porphyromonas gingivalis (P. gingivalis). Further analysis showed that W83, a reference strain previously reported to exhibit relatively high virulence-associated characteristics, produced significantly higher levels of indole than ATCC 33277 under the experimental conditions. Comparative genomic analysis of 36 complete P. gingivalis genomes showed that the amino acid sequences of TnaA were highly conserved. However, the transposase region adjacent to tnaA differed among strains: previously reported high-virulence strains, including W83, W50, and A7436, harbored the IS5-family transposase ISPg1, whereas several low-virulence reference strains carried the IS982-family transposase IS195. In saliva samples from periodontitis patients, ISPg1 expression was positively correlated with tnaA expression, and both were associated with periodontal clinical parameters. Together, these findings indicate that transposase-associated genomic variation near tnaA is associated with strain-specific tryptophan-indole metabolism, virulence-associated gene expression, and periodontal clinical parameters, while direct causality remains to be established in future functional studies.