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Ingredients of our daily diet鈥攊ncluding caffeine鈥攃an influence the resistance of bacteria to antibiotics. This has been shown in a new study by a team of researchers at the Universities of T眉bingen and W眉rzburg led by Professor Ana Rita Brochado. They discovered that bacteria such as Escherichia coli (E. coli) orchestrate complex regulatory cascades to react to chemical stimuli from their direct environment, which can influence the effectiveness of antimicrobial drugs.

In a systematic screening, Brochado's team investigated how 94 different substances鈥攊ncluding antibiotics, prescription drugs, and food ingredients鈥攊nfluence the expression of key gene regulators and transport proteins of the bacterium E. coli, a potential pathogen. Transport proteins function as pores and pumps in the bacterial envelope and control which substances enter or leave the cell. A finely tuned balance of these mechanisms is crucial for the survival of bacteria.

"Our data show that several substances can subtly but systematically influence gene regulation in bacteria," says Ph.D. student Christoph Binsfeld, first author of the study in PLOS Biology. The findings suggest even everyday substances without a direct antimicrobial effect鈥攅.g., caffeinated drinks鈥攃an impact certain gene regulators that control transport proteins, thereby changing what enters and leaves the bacterium.

"Caffeine triggers a cascade of events starting with the gene regulator Rob and culminating in the change of several transport proteins in E. coli鈥攚hich in turn leads to a reduced uptake of antibiotics such as ciprofloxacin," explains Ana Rita Brochado. This results in caffeine weakening the effect of this antibiotic. The researchers describe this phenomenon as an "antagonistic interaction."

This weakening effect of certain antibiotics was not detectable in Salmonella enterica, a pathogen closely related to E. coli. This shows that even in similar bacterial species, the same environmental stimuli can lead to different reactions鈥攑ossibly due to differences in transport pathways or their contribution to antibiotic uptake.

President Prof. Dr. Dr. h.c. (D艒shisha) Karla Pollmann states, "Such fundamental research into the effect of substances consumed on a daily basis underscores the vital role of science in understanding and resolving real-world problems."

The study makes an important contribution to the understanding of what is called "low-level" antibiotic resistance, which is not due to classic resistance genes, but to regulation and environmental adaptation. This could have implications for future therapeutic approaches, including what is taken during treatment and in what amount, and whether another drug or food ingredient should be given greater consideration.