Characterization of CETA and CETB, Energy Taxis Regulators in Campylobacter jejuni.

Abstract

Energy taxis is the ability of microbes to alter their direction of motility in response to changes in their local environment that affect energy-generating processes. The energy taxis receptor Aer, in Escherichia coli, senses changes in the electron transport system via an FAD cofactor bound to a PAS domain. The PAS domain is thought to interact directly with another Aer domain, the HAMP domain, to transmit a signal to the conserved signaling domain found in chemotaxis receptors. This work focused on an energy taxis system in Campylobacter jejuni composed of two proteins, CetA and CetB, each sharing specific domains with Aer. CetB has a PAS domain; CetA has a predicted transmembrane region, HAMP domain and signaling domain. We examined the expression of cetA and cetB, as well as the biochemical properties of the proteins they encode. cetA and cetB are co-transcribed independently of the flagellar regulon. Both CetA and CetB localize to the membrane and participate in complexes, including a likely CetB dimer and a complex that may include both CetA and CetB. HAMP domains, found in many bacterial signal transduction proteins, generally transmit an intramolecular signal between an extracellular sensory domain and an intracellular signaling domain. Studies of HAMP domains in proteins where both the input and output signals occur intracellularly are limited to Aer. The CetA HAMP domain differs significantly from that of Aer in predicted secondary structure. Similarity searches identified 55 pairs of HAMP/PAS proteins encoded by adjacent genes in a diverse group of microorganisms. We propose that these HAMP/PAS pairs form a new family of bipartite energy taxis receptors. Additionally, CetA contributes to C. jejuni invasion of human epithelial cells, while CetB does not, suggesting that members of HAMP/PAS pairs may act independently of each other. This work provides a framework for future studies into the molecular mechanism of signal transduction within CetA and CetB. Further, these studies suggest that the CetA/CetB system may be a widespread alternative to Aer with additional functional flexibility arising from a capacity for each protein to act independently to regulate traits other than energy taxis.