CemR atypical response regulator impacts energy conversion in Campylobacteria

Campylobacter jejuni and Arcobacter butzleri are microaerophilic food-borne human gastrointestinal pathogens of the Campylobacteria class. According to WHO, campylobacteriosis is the leading cause of diarrhoeal diseases, while A. butzleri is an emerging pathogen associated with diarrhoea, rapidly increasing in incidence worldwide. These species face different atmospheric conditions during infection and transmission, ranging from nearly anaerobic to aerobic conditions. Thus, they need to adjust their metabolism and respiration to the changing oxygen concentrations of the colonisation sites. Interestingly, no regulators redirecting energy conversion pathways in response to oxygen as an electron acceptor have been found in Campylobacteria (doi.org/10.1016/bs.ampbs.2019.02.003).

Our previous research on gastric human pathogen Helicobacter pylori, relative to C. jejuni and A. butzleri, revealed that the orphan response regulator HP1021 is a redox switch protein controlling the transcription of approx. 30% of genes (doi.org/10.1093/nar/gkab440, doi.org/10.1038/s41467-023-42364-6). The HP1021 regulon includes the tricarboxylic acid cycle (TCA) genes/proteins.

Here, we studied the regulons of HP1021 homologues in C. jejuni and A. butzleri, Cj1608 and Abu0127, respectively. We used RNA-seq and LC-MS/MS to identify genes/proteins regulated by Cj1608 and Abu0127 and define the Cj1608/Abu0127 dependent pathways used by C. jejuni and A. butzleri to respond to oxidative stress. We found that these regulators are involved in the control of more than 30% of genes in each species. The genes/proteins affected most in both species are related to metabolism and energy conservation processes, mostly TCA and electron transport chain. Using phenotypic analyses, we confirmed that energy conversion processes in Cj1608/Abu0127 deletion mutants are disturbed, which causes their delayed growth. Moreover, our combined data indicate that these regulators respond to oxygen levels and redirect metabolism towards optimal energy conservation. Thus, we named the proteins Campylobacteria energy and metabolism regulators – CemR.