Abstract

The evolution of antibiotic resistance in microorganisms is a major health issue. Understanding the evolutionary trajectories from susceptibility to resistance and the factors that affect it is crucial. Quantitative experiments and mathematical modelling can shed light on the processes that speed up or delay the evolution of resistance. We previously showed that tolerance, a form of survival under antibiotics that is distinct from resistance, plays a major role in promoting the evolution of resistance in vitro. In order to determine the relevance of the in vitro experimental evolution results for the clinic, we followed the course of infection in patients with life threatening bloodstream infections. A striking similarity between the in vitro and in host evolution is observed, despite the use in patients of combination therapy which was supposed to prevent resistance. Further dissection of the response of the clinical strains to combination of antibiotics reveals a new way by which resistance evolution is strongly promoted by the tolerance phenotype.