Novel transcriptional regulator OxtR1 regulates potential ferrodoxin in response to oxygen stress in Treponema denticola

• Published in: Anaerobe 2024-06, Vol.87, p.102852, Article 102852
• Main Authors: Numata, Yumi, Kikuchi, Yuichiro, Sato, Toru, Okamoto-Shibayama, Kazuko, Ando, Yutaro, Miyai-Murai, Yuri, Kokubu, Eitoyo, Ishihara, Kazuyuki
• Format: Article
• Language: English
• Subjects: Anaerobiosis; Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Gene Expression Profiling; Gene Expression Regulation, Bacterial; iron-sulfer cluster-binding protein; MarR; Microbial Sensitivity Tests; Oxidative Stress; Oxygen - metabolism; Oxygen stress; Promoter Regions, Genetic; Stress, Physiological; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional regulator; Treponema denticola; Treponema denticola - drug effects; Treponema denticola - genetics; Treponema denticola - growth & development; Treponema denticola - metabolism
• ISSN: 1075-9964; 1095-8274; 1095-8274
• DOI: 10.1016/j.anaerobe.2024.102852

Treponema denticola has been strongly implicated in the pathogenesis of chronic periodontitis. Previously, we reported that the potential transcriptional regulator TDE_0259 (oxtR1) is upregulated in the bacteriocin ABC transporter gene-deficient mutant. OxtR1 may regulate genes to adapt to environmental conditions during colonization; however, the exact role of the gene in T. denticola has not been reported. Therefore, we investigated its function using an oxtR1-deficient mutant. The growth rates of the wild-type and oxtR1 mutant were monitored under anaerobic conditions; their antibacterial agent susceptibility and gene expression were assessed using a liquid dilution assay and DNA microarray, respectively. An electrophoretic mobility shift assay was performed to investigate the binding of OxtR1 to promoter regions. The growth rate of the bacterium was accelerated by the inactivation of oxtR1, and the mutant exhibited an increased minimum inhibitory concentration against ofloxacin. We observed a relative increase in the expression of genes associated with potential ferrodoxin (TDE_0260), flavodoxin, ABC transporters, heat-shock proteins, DNA helicase, iron compounds, and lipoproteins in the mutant. OxtR1 expression increased upon oxygen exposure, and oxtR1 complementation suppressed the expression of potential ferrodoxin. Our findings also suggested that OxtR1 binds to a potential promoter region of the TDE_0259–260 operon. Moreover, the mutant showed a marginal yet significantly faster growth rate than the wild-type strain under H2O2 exposure. The oxygen-sensing regulator OxtR1 plays a role in regulating the expression of a potential ferrodoxin, which may contribute to the response of T. denticola to oxygen-induced stress. •oxtR expression increased responding to oxygen exposure•oxtR directly regulate potential ferredoxin and flavodoxin genes•Altered gene expression is observed in the oxtR mutant•oxtR influences antimicrobial susceptibility against ofloxacin•The growth rate of the oxtR mutant under oxygen stress is higher than that of wild type