The food-borne pathogen Campylobacter jejuni responds to the bile salt deoxycholate with countermeasures to reactive oxygen species

Bile plays an important role in digestion, absorption of fats, and the excretion of waste products, while concurrently providing a critical barrier against colonization by harmful bacteria. Previous studies have demonstrated that gut pathogens react to bile by adapting their protein synthesis. The ability of pathogens to respond to bile is remarkably complex and still incompletely understood. Here we show that Campylobacter jejuni, a leading bacterial cause of human diarrheal illness worldwide, responds to deoxycholate, a component of bile, by altering global gene transcription in a manner consistent with a strategy to mitigate exposure to reactive oxygen stress. More specifically, continuous growth of C. jejuni in deoxycholate was found to: 1) induce the production of reactive oxygen species (ROS); 2) decrease succinate dehydrogenase activity (complex II of the electron transport chain); 3) increase catalase activity that is involved in H2O2 breakdown; and 4) result in DNA strand breaks. Congruently, by adding 4-hydroxy-TEMPO (TEMPOL), a superoxide dismutase mimic, that reacts with superoxide to cultures under deoxycholate-mediated ROS stress, C. jejuni growth in the presence of deoxycholate was rescued. We postulate that continuous exposure of a number of enteric pathogens to deoxycholate stimulates a conserved survival response to this stressor. Overall design: Three C. jejuni strains were grown in Mueller-Hinton broth without deoxycholate for 12 hours, or with 0.05% deoxycholate for 14, 16, or 18 hours. Samples were generated in duplicate and transcriptional profiles of the different conditions and times were compared.