Choice of β-Lactam Resistance Pathway Depends Critically on Initial Antibiotic Concentration

Abstract

Antibiotic resistance trajectories with different final resistance may critically depend on the first mutation, due to epistatic interactions. Here, we study the effect of mutation bias and the concentration-dependent effects on fitness of two clinically important mutations in TEM-1 β-lactamase in initiating alternative trajectories to cefotaxime resistance.