Sometimes it really does take two. 

Scientists at Yerkes National Primate Research Center (YNPRC) at Emory University in Atlanta have discovered that a form of antibiotic resistance called “heteroresistance” is more widespread than previously thought, but attacking bacteria with combinations of antibiotics may hold the key to defeating them.

“We can think of heteroresistance as bacteria that are ‘half resistant’,” said David Weiss, PhD, director of the Emory Antibiotic Resistance Center, an associate professor of medicine (infectious diseases) and a researcher at the YNPRC. “This is because only some of the cells in the population exhibit resistance. When you take the antibiotic away, the resistant cells go back to being just a small part of the group. That’s why they’re hard to see in the tests that hospitals usually use.”

In exploring the heteroresistance phenomenon, Weiss and his colleagues examined 104 bacterial isolates, tracking multi-drug resistant superbugs. They found more than 85 percent were heteroresistant to at least two antibiotics. Weiss and his team then made their major discovery: Combining two antibiotics to which each superbug was heteroresistant proved effective at killing them. 

This occurred, they found, because the heteroresistant sub-populations were independent. If scientists grew the bacteria in the presence of one antibiotic, or knocked out resistance to that antibiotic genetically, this didn’t affect heteroresistance to any other antibiotics. 

Previously, microbiologists have thought some combinations of antibiotics might work together synergistically — one antibiotic working to weaken one part of the bacteria, while the other hits a different spot. But Weiss indicated the reasons combinations work might largely be explained by heteroresistance to multiple drugs. 

Using this knowledge, scientists are encouraged they will be able to help healthcare professionals more effectively use antibiotics to defeat bacteria that have developed resistance. 

“We’re saying: even if a strain of bacteria is classified as resistant to some antibiotics, don’t toss those drugs in the trash, they may still have some utility,” Weiss explained. “The ones targeting heteroresistance just have to be used in combination with others to do so.”