No Small Threat

Small populations of pathogenic bacteria may be harder to kill off than larger populations because they respond differently to antibiotics, a new Emory study finds.

Published in the journal eLife, the research shows that a population of bacteria containing one hundred cells or less responds to antibiotics randomly—not homogeneously like a larger population.

“We’ve shown that there may be nothing special about bacterial cells that aren’t killed by drug therapy—they survive by random chance,” says lead author Minsu Kim, an assistant professor in the Department of Physics and a member of Emory’s Antibiotic Resistance Center.

“This randomness is a double-edged sword,” Kim adds. “On the surface, it makes it more difficult to predict a treatment outcome. But we found a way to manipulate this inherent randomness in a way that clears a small population of bacteria with 100 percent probability. By tuning the growth and death rate of bacterial cells, you can clear small populations of even antibiotic-resistant bacteria using low antibiotic concentrations.”

The researchers developed a treatment model using a cocktail of two different classes of antibiotic drugs. They first demonstrated the effectiveness of the model in laboratory experiments on a small population of E. coli bacteria without antibiotic-drug resistance. In later experiments, they found that the model also worked on a small population of clinically isolated antibiotic-resistant E. coli.

“We hope that our model can help in the development of more sophisticated antibiotic drug protocols—making them more effective at lower doses for some infections,” Kim says. “It’s important because if you treat a bacterial infection and fail to kill it entirely, that can contribute to antibiotic resistance.”

Antibiotic resistance is projected to lead to 300 million premature deaths annually and a global health care burden of $100 trillion by 2050, according to the 2014 Review on Antimicrobial Resistance. The epidemic is partly driven by the inability to reliably eradicate infections of antibiotic-susceptible bacteria.