Regulatory involvement of the PerR and SloR metalloregulators in the oxidative stress response.

is a commensal of the human oral microbiome that can promote dental caries under conditions of dysbiosis. This study investigates metalloregulators and their involvement in the oxidative stress response. Oxidative stress in the human mouth can derive from temporal increases in reactive oxygen species (ROS) after meal consumption and from endogenous bacterial ROS-producers that colonize the dentition. We hypothesize that the PerR (SMU.593) and SloR (SMU.186) metalloregulatory proteins contribute to the regulation of oxidative stress genes and their products. Expression assays with UA159 wild type cultures exposed to HO reveal that HO upregulates , and that PerR represses transcription upon binding directly to Fur and PerR consensus sequences within the operator. In addition, the results of Western blot experiments implicate the Clp proteolytic system in SloR degradation under conditions of HO-stress. To reveal a potential role for SloR in the HO-resistant phenotype of GMS802 (a -deficient strain), we generated a / double knockout mutant, GMS1386, where we observed upregulation of the and antioxidant genes. These results are consistent with GMS802 HO resistance and with a role for PerR as a transcriptional repressor. Cumulatively, these findings support a reciprocal relationship between PerR and SloR during the oxidative stress response and begin to elucidate the fitness strategies that evolved to foster persistence in the transient environments of the human oral cavity.In 2020, untreated dental caries, especially in the permanent dentition, ranked among the most prevalent infectious diseases worldwide, disproportionately impacting individuals of low socioeconomic status. Untreated caries can lead to systemic health problems and has been associated with extended school and work absences, inappropriate use of emergency departments, and an inability for military forces to deploy. Together with public health policy, research aimed at alleviating induced tooth decay is important because it can improve oral health (and overall health), especially in underserved populations. This research, focused on metalloregulatory proteins and their gene targets, is significant because it can promote virulence gene control in an important oral pathogen, and contribute to the development of an anti-caries therapeutic that can reduce tooth decay.