Coffee perks you up – but it could also be energizing bacteria, making them more resistant to antibiotics. This is the unexpected finding from a team of researchers led by Professor Ana Rita Brochado at the University of Würzburg.
The study shows that certain food ingredients, including caffeine, make some antibiotics work less effectively. This doesn’t mean caffeine kills antibiotics directly. But it does cause subtle changes inside bacteria like E. coli.
These changes can block antibiotic entry, helping the bacteria survive. You won’t feel anything after that cup of tea, but the microbes in your gut might get more stubborn.
Bacteria notice what’s around them. They don’t just sit there waiting to die. E. coli, for example, reacts to chemical signals in its environment by flipping certain genes on or off. This gives it more control over what gets in and out of the cell.
Professor Brochado’s team tested 94 substances: antibiotics, human drugs, and common food ingredients.
The researchers focused on seven genes that affect transport proteins – tiny pores and pumps that regulate flow in and out of bacteria. Change these proteins, and you change how much antibiotic reaches the inside.
Some changes were big. Others were tiny. But one thing was clear: bacteria don’t treat caffeine like background noise.
The researchers found that caffeine activates a gene called Rob. Once Rob switches on, it sets off a chain reaction. Several transport proteins shift behavior, and the bacteria start blocking out antibiotics like ciprofloxacin.
“Caffeine triggers a cascade of events starting with the gene regulator Rob and culminating in the change of several transport proteins in E. coli, which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin,” explained Professor Brochado.
So caffeine doesn’t kill antibiotics. It just makes it harder for them to get inside the cell. The bacteria do not become fully resistant – they just become harder to kill.
The research suggests that bacteria can adapt based on diet and environment, even without new mutations or resistance genes.
“Our data show that several substances can subtly but systematically influence gene regulation in bacteria,” noted study lead author Christoph Binsfeld, a PhD student in the Department of Microbiology at the University of Würzburg.
The scary part? These effects don’t show up on standard resistance tests. You might think an antibiotic will work fine. But in your gut, after your morning coffee, bacteria might disagree.
You might expect this caffeine effect to happen across similar bacteria. But it doesn’t. The team also looked at Salmonella enterica, a close cousin of E. coli. Same antibiotic, same caffeine.
In Salmonella, caffeine didn’t reduce drug uptake. The difference likely comes down to how each species controls transport proteins. One tweaks the gates and the other doesn’t.
This shows that resistance isn’t just about which genes bacteria have. It’s also about how they use them – and when.
What Brochado’s team found isn’t classic resistance. There are no resistant genes being passed around and no permanent mutations. It’s something more flexible that bacteria can turn on or off.
Scientists call this “low-level” resistance. It’s temporary and subtle, but that doesn’t make it safe. It could help bacteria survive just long enough to cause a stubborn infection or evolve further resistance.
So, even though caffeine won’t make E. coli immortal, it might give it a fighting chance. And in medicine, even a small advantage can matter.
Bacteria like E. coli use regulators – proteins like MarA, SoxS, and Rob – to control responses. These proteins flip switches that change how transport proteins behave. In the study, Rob showed up more than expected.
Around one-third of all transcriptional changes involved Rob. That’s more than scientists thought. In many cases, Rob worked alongside MarA or SoxS. But in response to caffeine, Rob handled things on its own.
The researchers looked deeper and found something else. After caffeine exposure, over 200 bacterial proteins changed in abundance. That included proteins involved in building outer membrane pores. Less pore protein means fewer ways for antibiotics to get in.
“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 Dr. Karla Pollmann, President of the University of Tübingen.
If caffeine can influence antibiotic uptake, what about other compounds? What about patients drinking energy drinks or taking herbal supplements while on medication? These combinations might not be harmless.
Doctors might need to consider diet – including coffee – as part of treatment using antibiotics. Guidelines could eventually include not just dosage, but also what not to eat or drink during therapy.
The study is published in the journal PLOS Biology.
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