Streptococcus pneumoniaeaugments circadian clock gene expression in zebrafish cells

The circadian clock is a highly coordinated, cell-autonomous process that regulates the daily internal rhythms of biological organisms. Circadian clocks have been identified in various organisms, including mammals, invertebrates, cyanobacteria, and plants. The zebrafish (Danio rerio) is a practical model for studying the vertebrate circadian clock due to its small size, ease of manipulation, gene tractability, and direct light responsiveness. Several studies have revealed that bacterial, viral, and parasitic infections can impact the expression of circadian genes in mammals. While some evidence suggests that this may also be the case in zebrafish, no studies have investigated the direct effects of bacterial exposure on the zebrafish clock. Here, using zebrafish Z3 cells, we show that exposure to heat-killedStreptococcus pneumoniae(HK-Spn) can augment the expression of core repressive factors, includingper1b, per2, per3,andcry1a. Further investigation demonstrated that HK-Spn induces the production of reactive oxygen species (ROS) in Z3 cells and that the addition of NAC, a ROS antioxidant, blocks Spn-mediated induction ofper2,cry1a, andper3. Additionally, HK-Spn augmented the expression oftefaandtefb,an effect NAC suppressed. These results suggest the involvement of a ROS-dependent pathway in the augmentation ofper2,cry1a, and per3by HK-Spn. Moreover, the activation oftefaandtefbby HK-Spn represents promising new targets for further investigation of the regulation of these genes.