Antibiotic tolerance facilitates the evolution of resistance

TLDR

Bacterial survival under antibiotics can arise from tolerance—quiescence during high drug exposure—or from active resistance mechanisms, both driven by mutations from the wild type. The study argues that tolerance, often overlooked clinically, should be screened and targeted to curb the emergence of resistance. Tolerant cells survive longer, increasing the likelihood of acquiring resistance mutations. In vitro evolution experiments showed that ampicillin resistance develops most rapidly in populations with pre‑existing tolerance mutations. Levin‑Reisman et al., Science, this issue p.

Abstract

Resistance on a background of tolerance Bacteria survive antibiotic exposure either because they are quiescent when antibiotics are around in the highest concentrations (i.e., tolerance) or because they acquire active biochemical resistance mechanisms (i.e., resistance). Both tolerance and resistance involve the acquisition of mutations from the wild type. Levin-Reisman et al. used in vitro evolution experiments to show that populations of bacteria that become genetically resistant to the antibiotic ampicillin most quickly do so on a background of tolerance mutations (see the Perspective by Lewis and Shan). Because the probability of a tolerant organism surviving is higher, it has a greater chance of subsequently acquiring resistance mutations. Tolerance is often overlooked in the clinic but should in future be screened for and targeted more precisely to reduce the rates of acquired resistance. Science , this issue p. 826 ; see also p. 796