The team hypothesized that the second drug restored the cellular equilibrium that the first drug distorted. This enabled the bacteria to flourish in the midst of this dual-antibiotic assault, though it isn't yet mechanistically clear why.

To corroborate these initial findings, the team conducted a second round of experiments in which they impaired the ability of E. coli to produce ribosomes. As a result, the cells could more easily withstand the assault of the first drug, yet succumbed to the second, completely removing the strong antagonism between the drugs.

This work "suggests that there are things about antibiotics and other inhibitors that we never suspected," said University of British Columbia microbiologist Julian Davies, "We are so naive about how drugs work. We are so naive about the activities of these compounds once they are actually in human beings. What I think will be important about this work is that people will be able to design model studies with animals. If one can reproduce these results in animal models, they could be adapted to a human situation."

The discovery has inspired Kishony and his team to ask a more general question about antibiotic interactions. Kishony recently received a federal stimulus grant to pursue a study that explores the genetic determinants of drug interactions more broadly and investigates whether cells can be synthetically manipulated to change the way drugs interact.

"Understanding how cells alter their genetic programs in the presence of antibiotic drugs could provide insights into new ways to discourage the growth of pathogens and encourage the growth of 'good' bacteria in the lab and in the clinic," said Kishony.

Source: Harvard Medical School