Antibiotic resistance is a serious worldwide threat to public health, with reports predicting drug-resistant infections will claim the lives of 10 million people each year by 2050. Antibiotics have come a long way since they revolutionized medicine in the 20th century, when they fought off bacterial infections like tuberculosis and strep throat — both were once fearsome illnesses. Today, due to overconsumption and frequent misuse, resistant bacteria have rendered certain antibiotics useless for treating specific illnesses. New research published in Nature Microbiology, however, calls into question the effectiveness of antibiotics even when there are no resistant bacteria involved.

The study, led by researchers from Katholieke Universiteit Leuven in Belgium, found that each time bacteria are subjected to antibiotics, more of them survive. Moreover, they even develop a tolerance to multiple drugs. Unlike resistant bacteria, these bacterial cells cannot continue growing during an antibiotic treatment. However, they can survive the antibiotic treatment and resume their reproduction when the treatment is finished. Because of their persistence, researchers have called these cells “persister cells.”

“Multi-drug tolerance in bacteria not only relies on the build-up of resistance mutations, but also on some cells epigenetically switching to a non-growing antibiotic-tolerant ‘persister’ state,” researchers wrote. “Yet, despite its importance, we know little of how persistence evolves in the face of antibiotic treatment.”

Researchers studied the gut bacteria E. Coli to examine this phenomenon in which the non-resistant bacteria flare up following a course of treatment. After treating the bacteria with daily antibiotic doses in the lab, they found that although most of the gut bacteria were initially killed, some E. Coli survived the treatment in a dormant state. Once treatment stopped, these dormant cells found a way “to adapt with minimal changes in their genetic material,” become active again, and recolonize the body, researchers wrote. This results in the rapid development of many persister cells.

"These tolerant cells can just sit out treatment,” researcher Joran Michiels said in a statement. "On the first day of treatment, they are already present, albeit in small numbers. They ensure that the population is not wiped out and that it can be reconstituted after the antibiotic treatment. Eventually, you end up with an entire population that is tolerant to several antibiotics."

Overall, the study shows that how often bacteria is exposed to antibiotics correlates with an increase in the number of tolerant cells. Taking one antibiotic a day has a bigger impact on this expansion than weekly doses. Fortunately, researchers found that these tolerance cells reduce in number as soon as antibiotic treatment ends.

"It is common practice to screen for resistance during antibiotic treatments, but not for tolerance. And yet, tolerant bacteria can go on to develop antibiotic resistance, which adds to the global antibiotic crisis: the development of new antibiotics cannot keep pace with the growing antibiotic resistance of bacteria,” Michiels said. “Therefore, figuring out how and why more bacteria develop antibiotic tolerance is important to improve future therapies and thus save lives.”

Source: Van den Bergh B, Michiels J, Wenseleers T, et al. Frequency of antibiotic application drives rapid evolutionary adaptation ofEscherichia coli persistence. Nature Microbiology. 2016.