# The unique histidine kinase, AtcS, regulates motility and pathogenicity of the periodontal pathobiont, Treponema denticola

## TL;DR

The study shows that the AtcS histidine kinase is crucial for the movement and disease-causing ability of Treponema denticola, a bacterium linked to periodontal disease.

## Contribution

This study identifies AtcS as a key regulator of motility and pathogenicity in Treponema denticola through transcriptomic and functional analyses.

## Key findings

- Deletion of atcS reduces transcription of genes related to motility and dentilisin protease complex.
- The atcS-deficient strain shows reduced dentilisin activity, motility, and ability to invade host cells.
- The mutant fails to induce alveolar bone loss in a mouse model of periodontitis.

## Abstract

Treponema denticola 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 T. denticola to thrive and cause disease. Yet, our understanding of T. denticola 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 T. denticola adaptive responses has not been investigated. To address this knowledge gap, we constructed a deletion of the atcS gene, encoding the histidine kinase. We performed RNA sequencing, demonstrating that the deletion of atcS results in significant changes in the transcriptome of T. denticola. 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 T. denticola. This aligns with our observation that the atcS-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 T. denticola virulence. This study is a significant step toward defining the role of the AtcSR two-component system in T. denticola pathogenicity.