New research suggests small populations of pathogenic bacteria may be harder to kill off than larger populations due to the random response of 100 cells or less to antibiotic treatment. The study was published in the journal eLife.

For decades, it was thought that reducing bacterial population size to a few hundred cells would be enough for the immune system to take over and clear the disease. However, that thinking has changed based on observations that small populations of bacteria can cause serious infection—even populations in the tens of cells or lower.

Why some bacteria populations are wiped out in low numbers and some can remain highly infectious was unclear. Minsu Kim, an assistant professor in the Department of Physics and a member of Emory's Antibiotic Resistance Center suspected there was something fundamental to the nature of bacteria that caused this uncertainty.

He and other Emory researchers looked at the dynamics of small populations as compared to large ones following antibiotic treatment. They found that antibiotics can cause bacterial concentrations to fluctuate. When the growth rate topped the death rate by random chance, clearance of the bacteria failed.

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They applied this knowledge to develop a new low-dose treatment that combines a bacteriacide (to kill bacteria) with a bacteristat (that slows bacterial growth) to manipulate the random fluctuation in the number of cells and increase the chances that cell death rate will top the growth rate.

The treatment model worked in a small population of E. coli bacteria without antibiotic-drug resistance and in a small resistant population of E.coli. However, not all antibiotics were found to fit the model and more research is needed to apply these findings to a clinical setting.

"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."