Gram-negative bacteria like E. coli have built-in gatekeepers, porins, and pumps that decide what gets in or out, including antibiotics. The bacteria's genetic control room tightly regulates these microscopic bouncers. But we still don't fully understand how chemicals, like food ingredients or medications, tweak these systems.
A new study by the University of Tübingen researchers has cracked open this mystery by testing E. coli bacteria in 94 different chemical environments. Researchers focused on seven key transport-related genes and uncovered some unexpected influencers, not just antibiotics, but everyday compounds like caffeine.
Turns out, E. coli isn't just reacting to drugs, it's constantly scanning its surroundings and adjusting its defenses. Even natural substances can flip bacterial “alert switches,” reshaping how they respond to treatment.
This insight could help scientists fine-tune therapies by factoring in not just the medicine, but the chemical context around it, from diet to drug combos.
Led by researcher Ani Rita Brochado, a team carefully tested 94 different substances like antibiotics, medicines, and food ingredients to see how they affect E. coli, a type of bacteria that can sometimes make people sick. They examined how these substances altered the activity of specific genes and proteins that enable bacteria to regulate what enters and exits their cells.
"Our data show that several substances can subtly but systematically influence gene regulation in bacteria," explained Christoph Binsfeld, first author of the study.
The findings suggest even everyday substances without a direct antimicrobial effect, such as caffeinated drinks, can impact certain gene regulators that control transport proteins, thereby changing what enters and exits 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, which in turn leads to a reduced uptake of antibiotics such as ciprofloxacin," said Ana Rita Brochado.
This phenomenon is recognized as an "antagonistic interaction."
And perhaps most interestingly, not all bacteria responded to caffeine the same way. Even though Salmonella enterica is a close cousin of E. coli, it didn't flinch when exposed to the same combination of caffeine and antibiotics that rattled E. coli. That's proof that similar bacteria don't always behave the same way.
This unexpected finding suggests Salmonella may use different routes to move molecules in and out. And this means it might not let antibiotics in as easily, or it might not react the same way when it does.
The new study, published in PLOS Biology, sheds light on a subtle but important form of antibiotic resistance, called low-level resistance. Unlike the usual suspects (classic resistance genes), this kind doesn't come from mutations. Instead, it's shaped by how bacteria adjust to their environment and regulate their internal systems.
That means what we eat, what drugs we take, and even the timing or combination of treatments could influence how bacteria respond. A food ingredient like caffeine or a second medication might tip the balance, making antibiotics more or less effective.
It’s not just about the drug; it's about the whole chemical conversation happening around it.
The new study was published in PLOS Biology.
Source: University of Tübingen
