Periodontitis is an infectious disease caused by bacteria in subgingival plaque, leading to the loss of the periodontal ligament and alveolar bone that supports teeth [1]. Dysbiosis, characterized by a shift in the subgingival microbiome composition, has been suggested as a significant factor contributing to periodontitis [2]. Treponema denticola is an intermediate-sized anaerobic oral spirochete that requires serum for growth, and it is highly resistant to refampin [3]. This microorganism is significantly increased in periodontitis lesions [4]. This microorganism possesses various virulence factors, including the surface protease dentilisin, factor H-binding protein B, and major outer sheath protein (Msp) [5]. Multiple microbiome analyses of chronic periodontitis lesions indicated that T. denticola is a marker microorganism for dysbiosis [6], indicating its involvement in dysbiosis within subgingival plaques. To colonize and thrive in dental plaque, T. denticola must regulate genes to adapt to rapidly changing environmental conditions, such as oxygen concentration variations [7], pH fluctuations, and antimicrobial agents. While gene regulation mechanisms have been reported in T. denticola under co-incubation with other species [8] and during metal ion uptake via the regulation of the TroR operon [9], sensing of hemin by the PAS domain-containing histidine kinase (Hpk2) [10], and regulation of motility and biofilm formation by cyclic di-GMP [11], a comprehensive understanding of its response to environmental conditions is lacking.

We previously reported decreased susceptibility against chloramphenicol and ofloxacin in an inactivated bacteriocin ABC transporter-like gene (tepA2) mutant and increased expression of TDE_0259 (oxtR1), a gene with similarity to the multiple-antibiotic resistance regulator (marR) gene [12]. The MarR family genes possess a receptor domain to sense chemical stimuli and DNA binding motifs with helix-turn-helix structures [13]. MarR members regulate gene expression by modulating DNA-binding affinity upon signal presence/absence by allostery. In addition, the MarR family regulates genes involved in resistance to multiple antibiotics, organic solvents, oxidative stress agents, and pathogenic factors [14]. TDE_0259 likely responds to stress induced by tepA2 inactivation; however, its specific role in environmental adaptation within T. denticola remains to be elucidated.

In this study, we aimed to investigate the function of OxtR1 in T. denticola, particularly in response to environmental stress, using an OxtR1-deficient mutant and clarified its involvement in response to oxygen stress. We believe that our findings could help elucidate the vital role of OxtR1 in T. denticola, notably in its adaptation to oxygen-induced stress, and contribute to a better understanding of its environmental response mechanisms in the process of dysbiosis, which is characterized by a shift in microbiome composition in the subgingival area.