Proteome Profiling by Label‐Free Mass Spectrometry Reveals Differentiated Response of Campylobacter jejuni 81–176 to Sublethal Concentrations of Bile Acids

PURPOSE: Bile acids are crucial components of the intestinal antimicrobial defense and represent a significant stress factor for enteric pathogens. Adaptation processes of Campylobacter jejuni to this hostile environment are analyzed in this study by a proteomic approach. EXPERIMENTAL DESIGN: Proteome profiling by label‐free mass spectrometry (SWATH‐MS) has been used to characterize the adaptation of C. jejuni to sublethal concentrations of seven bile acids. RESULTS: The bile acids with the lowest inhibitory concentration (IC(50)), deoxycholic and chenodeoxycholic acid, induce the most significant proteome changes. Overall a downregulation of all basic biosynthetic pathways and a general decrease in the transcription machinery are found. Concurrently, an induction of factors involved in detoxification of reactive oxygen species, protein folding, and bile acid exporting efflux pumps is detected. Exposure to deoxycholic and chenodeoxycholic acid results in an increased expression of components of the more energy‐efficient aerobic respiration pathway, while the anaerobic branches of the electron transport chain are down‐expressed. CONCLUSIONS AND CLINICAL RELEVANCE: The results show that C. jejuni has a differentiated system of adaptation to bile acid stresses. The findings enhance the understanding of the pathogenesis of campylobacteriosis, especially for survival of C. jejuni in the human intestine, and may provide clues to future medical treatment.