Long-term evolution of antibiotic persistence in P. aeruginosa lung infections

Abstract

AbstractPathogenic bacteria respond to antibiotic pressure with the evolution of resistance but survival can also depend on their ability to tolerate antibiotic treatment, known as persistence. While a variety of resistance mechanisms and underlying genetics are well characterised in vitro and in vivo, the evolution of persistence, and how it interacts with resistance in situ is less well understood. We assayed for persistence and resistance with three clinically relevant antibiotics: meropenem, ciprofloxacin and tobramycin, in isolates of Pseudomonas aeruginosa from chronic cystic fibrosis lung infections spanning up to forty years of evolution. We find evidence that persistence is under positive selection in the lung and that it can particularly act as an evolutionary stepping stone to resistance. However, this pattern is not universal and depends on the bacterial clone type and antibiotic used, indicating an important role for antibiotic mode of action.