Antibiotics: Combatting Tolerance To Stop Resistance

Abstract

Antibiotic resistance poses an alarming and ever-increasing threat to modern health care. Although the current antibiotic crisis is widely acknowledged, actions taken so far have proved insufficient to slow down the rampant spread of resistant pathogens. Problematically, routine screening methods and strategies to restrict therapy failure almost exclusively focus on genetic resistance, while evidence for dangers posed by other bacterial survival strategies is mounting. Antibiotic tolerance, occurring either population-wide or in a subpopulation of cells, allows bacteria to transiently overcome antibiotic treatment and is overlooked in clinical practice. In addition to prolonging treatment and causing relapsing infections, recent studies have revealed that tolerance also accelerates the emergence of resistance. These critical findings emphasize the need for strategies to combat tolerance, not only to improve treatment of recurrent infections but also to effectively address the problem of antibiotic resistance at the root.

Keywords: antibiotic resistance; antibiotics; evolution; persistence.

FIG 1

Framework for how antibiotic tolerance and persistence accelerate the evolution of genetic resistance. First, in populations displaying high levels of tolerance or persistence, an increased number of viable cells is available for mutation, increasing the likelihood for a resistant mutant to arise. Second, persistence is linked with higher mutation rates, again causing an increased likelihood for the occurrence of resistance-conferring mutations. Future research will reveal if a similar link exists between tolerance and mutation rates.