A recent study unveils a surprising mechanism: antibiotics, designed to eliminate bacteria, can paradoxically boost their survival and accelerate the development of drug resistance. Understanding this process is crucial for improving antibiotic strategies and combating the growing threat of antibiotic-resistant infections, which affect millions globally.
Researchers at Rutgers Health have discovered that the common antibiotic ciprofloxacin, used to treat urinary tract infections, can trigger an energy crisis in Escherichia coli (E. coli) bacteria. This crisis, however, doesn't kill the bacteria as intended. Instead, it prompts them to adapt and become more resistant to the drug.
The study, published in Nature Communications, focused on adenosine triphosphate (ATP), the energy source for cells. When ciprofloxacin disrupts ATP levels, the bacteria experience "bioenergetic stress." Surprisingly, the bacteria respond by increasing their respiration and producing reactive oxygen molecules, which damage their own DNA. This leads to two significant outcomes.
First, more bacteria survive. Stressed cells, known as persister cells, can withstand lethal doses of the antibiotic. These cells lie dormant until the drug is gone, then rebound to cause new infections. Secondly, the stressed bacteria mutate faster, developing resistance to the antibiotic. This accelerated mutation is linked to oxidative damage and errors in DNA repair.
The findings suggest that the metabolic changes induced by antibiotics make them less effective and promote resistance. The researchers also found that other antibiotics, such as gentamicin and ampicillin, have a similar effect. This could have implications for treating various infections, including those caused by Mycobacterium tuberculosis.
This research highlights the need to rethink how antibiotics are developed and used. Potential strategies include screening new antibiotics for energy-drain side effects, combining existing drugs with agents that block stress pathways, and reconsidering the use of high doses. By understanding and addressing the metabolic responses of bacteria, we can improve the effectiveness of antibiotics and combat the rise of drug-resistant infections.