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Antibiotic Interactions

07/13/2015
Kayt Sukel

Can a better understanding of the molecular workings of antibiotic drugs help us fight the growing problem of antibiotic resistance? Researchers at the Broad Institute think so. Learn more...


According to the Centers for Disease Control and Prevention (CDC), at least 2 million people are infected each year with bacteria that are resistant to antibiotic treatment—and more than 20,000 of those individuals will die from those infections. Experts agree that the problem of antibiotic resistance is growing, but how and why remain unclear.

“We’ve been using antibiotic drugs for more than 50 years. So while we definitely have some understanding of how they work, we’ve allowed that understanding to pass as a comprehensive understanding. And we really don’t have that comprehensive understanding,” said James J. Collins, a professor of bioengineering at the Broad Institute of MIT & Harvard University. “We hypothesized that these drugs were likely doing more than suspected. But we set out several years ago to see if we could expand our knowledge by using systems biology approaches and gain a better understanding of how some of these bugs are becoming resistant to the drugs.”

Source: PNAS

Collins and his team showed that bactericidal antibiotics accelerate cellular respiration, the metabolic processes that convert nutrients into biochemical energy, downstream of their drug–target interactions. But the team wondered if other antibiotics worked in the same manner. Would bacteriostatic drugs, which slow bacterial growth and reproduction, show similar elevated respiration? In a new study published in PNAS, the researchers measured oxygen consumption in bacteria after they were treated with the two different classes of drugs, alone and in combination. They found that bacteriostatics, unlike bactericidals, actually inhibited cellular respiration.

“We’ve provided mechanistic insight into why, when you combine a bacteriostatic antibiotic with a bactericidal antibiotic, you will often eliminate the killing effects that would result from a bactericidal antibiotic alone. The bacteriostatic inhibition of cellular respiration effect dominates,” said Collins. “Going further, if you give the bacteriostatic antibiotic after the bactericidal antibiotic, you can halt the killing. So our work provides guidance for combinations of antibiotics, especially when treating a resistant infection. If the goal is to kill the bacteria, you have to be careful not to include a static antibiotic.”

These results can also help boost the power of existing antibiotic drugs to fight the growing problem of antibiotic resistance. “We show, using genetic experiments, that if you enhance cellular respiration, you can enhance the killing effect of a bactericidal antibiotic,” he said. “So it points to new ways we can improve the antibiotic arsenal we already have at our disposal to more effectively fight those really resistant bacteria.”

Reference

Lobritz MA, Belenky P, Porter CB, Gutierrez A, Yang JH, Schwarz EG, Dwyer DJ, Khalil AS, Collins JJ. Antibiotic efficacy is linked to bacterial cellular respiration. Proc Natl Acad Sci U S A. 2015 Jun 22.

Keywords:  antibiotics