Researchers from the University of Tübingen and the University of Würzburg have found that ingredients of our daily diet — including caffeine — can influence the resistance of bacteria to antibiotics; they’ve discovered that bacteria such as Escherichia coli orchestrate complex regulatory cascades to react to chemical stimuli from their direct environment which can influence the effectiveness of antimicrobial drugs.
This illustration depicts a 3D computer-generated image of a group of Escherichia coli. Image credit: James Archer, CDC.
In a systematic screening, Professor Ana Rita Brochado and colleagues investigated how 94 different substances — including antibiotics, prescription drugs, and food ingredients — influence the expression of key gene regulators and transport proteins of Escherichia coli bacteria.
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,” said Ph.D. student Christoph Binsfeld.
“The findings suggest even everyday substances without a direct antimicrobial effect — e.g. caffeinated drinks — can 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 Escherichia coli — which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin,” Professor Rita Brochado added.
“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 Escherichia coli.
This shows that even in similar bacterial species, the same environmental stimuli can lead to different reactions — possibly due to differences in transport pathways or their contribution to antibiotic uptake.
“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,” said Professor (Dōshisha) Karla Pollmann.
“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.”
The results appear online in the journal PLoS Biology.
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C. Binsfeld et al. 2025. Systematic screen uncovers regulator contributions to chemical cues in Escherichia coli. PLoS Biol 23 (7): e3003260; doi: 10.1371/journal.pbio.3003260