The problem of antibiotic resistance has become a persistent one in recent times, as overuse of antibiotics had led to pathogenic bacteria becoming able to adapt to the new environment and beginning to thrive again.
Now, a new study, published in the Proceedings of the National Academy of Sciences, a team at Harvard’s Wyss Institute for Biologically Inspired Engineering, led by James Collins, PhD, has pinpointed a critical differentiator that separates the effects of bactericidal and bacteriostatic antibiotics: cellular respiration. This metabolic process uses oxygen under aerobic conditions to convert energy stored in nutrients into ATP, the main energy currency used by all cells.
Michael Lobritz, the study’s first author and a Clinical Fellow at Wyss, said: “It was known for a while that some bactericidal antibiotics put bacterial respiration into over-drive, which, by producing too many oxygen radicals, become toxic to the pathogens.
“We wanted to zero in on these bacterial responses and decided to systematically investigate respiration levels in bacteria treated with a larger spectrum of bactericidal and bacteriostatic antibiotics.”
Observing that bacteriostatic antibiotics slowed down oxygen consumption and energy production in cellular respiration, the team found that bacteriostatic respiratory outcomes always dominated meaning that the net effect always is a reduction in cellular respiration. As a result, bactericidal effects get eliminated in the mix and the pathogenic bacteria become tolerant.
Dr Collins commented: “Adding bacteriostatic antibiotics to a combination induces bacterial tolerance to the bacteriocidal treatment. This could help explain why certain antibiotic therapies do not work. Elucidating the pathways that mediate changes in respiration triggered by specific antibiotics could lead to new potential drug targets that may help achieve the same result in infected patients.
“These findings are only the beginning. They show that better combinations of antibiotics are possible. But ultimately we want to gain deeper insight into the antibiotic modes of action affecting cellular respiration so we can identify better antibiotics to help treat infections.”