Peter Belenky is assistant professor of molecular microbiology and immunology at Brown University. He was the lead author of a recent study on the surprising complexity of antibiotic functionality in the journal Cell Reports. The paper is part of the worldwide effort to prevent the efficacy of antibiotics from descending to dangerously low levels.
PBN: Most well-informed adults think they understand, generally at least, how antibiotics function. What are some of the ways that both the general public, and science, have misunderstood the way antibiotics actually work?
BELENKY: The most common misconception among the public is that antibiotic therapy works by specifically killing the bacteria causing the infection. The reality is that antibiotics are much less specific, killing both the bad and the good bacteria that reside in all of us.
The most common scientific misconception is that antibiotics kill bacteria by blocking some very particular bacterial processes. We think that antibiotic-induced death is much more complicated and that antibiotics induce many different forms of damage that then cumulatively kill bacteria. Thus antibiotic-induced death in bacteria is more akin to death by a thousand cuts than by one single blow.
PBN: Your study addresses antibiotic resistance. What is a worst-case scenario when it comes to antibiotics’ diminishing efficacy?
BELENKY: I do not believe that we will get to the worst-case scenario because the medical community is responding to the crisis by regulating antibiotic use while simultaneously research such as ours is developing novel strategies for more effective use of current and new antibiotics. However, if not for these efforts, the worst-case scenario would be that by 2050 we would have approximately 300,000 to 400,000 deaths related to antimicrobial resistance in North America alone (currently the number is around 40,000), killing more people than cancer. The other and perhaps more dire consequence is that without effective antimicrobial therapy, routine medical procedures such as C-sections and other minor surgeries will become impossible due to the unacceptably high risk of untreatable infections. If unchecked, the antibiotic resistance crisis could lead to the first major reduction in overall life expectancy in the developed world.
PBN: How do antibiotics affect DNA, and how is that contributing to antibiotic resistance?
BELENKY: We have found that certain antibiotics, especially when given at non-therapeutic amounts, can damage bacterial DNA directly and also lead to other processes that elevate the chance of getting mutations. Most of these mutations will have no benefit for the bacteria, but some will provide a level of protection from the antibiotic. Thus, each use of antibiotics has a very tiny chance of inducing the development of resistance. Multiply that over the millions of doses given each year and you can see how resistance can evolve. Knowing this can help regulate the use of antibiotics to reduce the chance of developing resistance.
PBN: What is bacterial metabolism, and what role does it play in the efficacy of antibiotics?
BELENKY: Just like us, bacteria take in nutrients and use that energy to live and multiply. In our work we found that antibiotics force bacteria to put this metabolic activity into “overdrive,” which leads to numerous toxic side effects that may contribute to bacterial death. This observation indicates that the artificial induction of bacterial metabolism may provide an intervention to make current antibiotics more potent.
PBN: What is the next step in your research?
BELENKY: Most antibiotic research currently takes place in the lab and uses a select set of easy-to-study bacteria. However, in reality antibiotics given to people actually impact the trillions of beneficial and pathogenic bacteria that live inside all of us, called the microbiome. The next step for us is to study how antibiotics function in actual patients and to profile the impact of antibiotics on the microbiome. The ultimate goal is to develop therapies that have fewer side effects and reduce the chance of developing resistance.