Profiling of the Helicobacter pylori redox switch HP1021 regulon using a multi-omics approach

The gastric human pathogen Helicobacter pylori has developed mechanisms to combat stress factors, including reactive oxygen species (ROS). Here, we present a comprehensive study on the redox switch protein HP1021 regulon combining transcriptomic, proteomic and DNA-protein interactions analyses. Our results indicated that HP1021 modulates H. pylori's response to oxidative stress. HP1021 controlled the transcription of 497 genes, including 407 genes related to response to oxidative stress. 79 proteins were differently expressed in the HP1021 deletion mutant. HP1021 regulated typical ROS response pathways (katA, rocF) and less canonical ones, particularly DNA uptake and central carbohydrate metabolism. We identified HP1021 as the first molecular regulator of competence in H. pylori, as HP1021-dependent repression of the comB DNA uptake genes was relieved under oxidative conditions, increasing natural competence. Furthermore, HP1021 controlled glucose consumption by directly regulating the gluP transporter and had an important impact on maintaining the energetic balance in the cell.