The Campylobacter jejuni RacRS system regulates fumarate utilization in a low oxygen environment.
The natural environment of the human pathogen Campylobacter jejuni is the gastrointestinal tract of warm-blooded animals. In the gut, the availability of oxygen is limited; therefore, less efficient electron acceptors such as nitrate or fumarate are used by C. jejuni. The molecular mechanisms that regulate the activity of the highly branched respiratory chain of C. jejuni are still a mystery mainly because C. jejuni lacks homologues of transcription factors known to regulate energy metabolism in other bacteria. Here we demonstrate that dependent on the available electron acceptors the two-component system RacRS controls the production of fumarate from aspartate, as well as its transport and reduction to succinate. Transcription profiling, DNAse protection and functional assays showed that phosphorylated RacR binds to and represses at least five promoter elements located in front of genes involved in the uptake and synthesis of fumarate. The RacRS system is active in the presence of nitrate and trimethyl-amine-N-oxide under oxygen-limited conditions when fumarate is less preferred as an alternative electron acceptor. In the inactive state, RacRS allows utilization of fumarate for respiration. The unique C. jejuni RacRS regulatory system illustrates the disparate evolution of Campylobacter and aids the survival of this pathogen.
Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, 3584CL, The Netherlands.
Anne-Xander
AX
van der Stel
Andries
A
van Mourik
Linda
L
Heijmen-van Dijk
Craig T
CT
Parker
David J
DJ
Kelly
Chris H A
CH
van de Lest
Jos P M
JP
van Putten
Marc M S M
MM
Wösten
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics; D016123:Campylobacter jejuni / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000235:genetics; D004579:Electron Transport / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005650:Fumarates / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D009566:Nitrates / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D005650:Fumarates; D009566:Nitrates; C119362:RacR protein, Campylobacter jejuni; D012097:Repressor Proteins; D015534:Trans-Activators; D019802:Succinic Acid; D010100:Oxygen