Mechanism of how Campylobacter jejuni mediates protection from bile acid stress (ProBAS) to co-cultivated bacteria

• Applicant: Professor Dr. Uwe Groß, since 8/2022
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 428673465

Bile acids pose a significant stress factor for intestinal bacteria and lead to adaptation processes for survival in the intestine. We observed a novel interbacterial interaction during co-cultivation of intestinal Campylobacter species with Enterococcus faecalis and Staphylococcus aureus in the presence of bile acids. This interaction requires a direct cell-to-cell contact between Campylobacter and the target bacteria, is mediated by soluble proteins, and finally leads to survival of E. faecalis and S. aureus from otherwise lethal concentrations of deoxycholate (DCA). The term “ProBAS” (protection from bile acid stress) was introduced to describe this effect. We seek to unravel in this application the molecular mechanisms that lead to ProBAS. One major aim is the identification of the putatively secreted, ProBAS-mediating C. jejuni proteins from cell-free supernatants with the aid of mass spectrometry. The corresponding genes of the identified proteins will be deleted in C. jejuni and the generated mutants will be tested in co-cultivation experiments for their potential to mediate ProBAS. Moreover, Transcriptomic and proteomic studies on S. aureus and E. faecalis will be performed after incubation with the ProBAS-mediating supernatant of a Campylobacter-broth culture, in order to understand the physiological basis that leads to increased bile acid resistance. In particular, we will investigate, whether ProBAS is associated with an increased resistance to other stress factors, as for example exposure to reactive oxygen species (ROS). Furthermore, we will use the obtained transcriptomic and proteomic data to analyse the activation processes that occur in C. jejuni itself, after direct cell-to-cell contact with E. faecalis and S. aureus. In summary, the proposed studies will lead to a better understanding of a novel and unexpected interbacterial interaction process.

• DFG Programme: Research Grants
• Co-Investigators: Dr. Wolfgang Bohne; Dr. Raimond Lugert
• Ehemaliger Antragsteller: Professor Dr. Andreas Zautner, until 8/2022