The unique histidine kinase, AtcS, regulates motility and pathogenicity of the periodontal pathobiont, <i>Treponema denticola</i>

<i>Treponema denticola</i> is an obligate colonizer of the human gingival crevice and, along with other pathobionts, is highly associated with the development of periodontal disease. As periodontal disease develops, significant environmental changes occur in the subgingival crevice and oral microbiome. The ability to sense and respond to changing environmental conditions is essential to the ability of <i>T. denticola</i> to thrive and cause disease. Yet, our understanding of <i>T. denticola</i> sensory transduction and gene regulatory mechanisms is nearly absent. The AtcSR two-component system has been predicted to regulate several cellular processes, but its role in <i>T. denticola</i> adaptive responses has not been investigated. To address this knowledge gap, we constructed a deletion of the <i>atcS</i> gene, encoding the histidine kinase. We performed RNA sequencing, demonstrating that the deletion of <i>atcS</i> results in significant changes in the transcriptome of <i>T. denticola</i>. Most notably, the transcription of genes encoding proteins involved in motility and the dentilisin protease complex was reduced. Consistent with this, the deletion mutant displayed reduced dentilisin activity and motility. These phenotypes are critical to interactions with host cells and the pathogenicity of <i>T. denticola</i>. This aligns with our observation that the <i>atcS</i>-deficient strain had attenuated attachment and invasion of gingival epithelial cells and failed to induce alveolar bone loss in a murine periodontitis model, processes that are central to <i>T. denticola</i> virulence. This study is a significant step toward defining the role of the AtcSR two-component system in <i>T. denticola</i> pathogenicity.