The Effect of the Stringent Response and Oxidative Stress Response on Fitness Costs of De Novo Acquisition of Antibiotic Resistance

• DOI: 10.20944/preprints202311.0657.v1
• Publication Date: 2023-11-10T08:45:17Z
• Authors: Wenxi Qi; Drosos Katsavelis; Wim De Leeuw; Meike T. Wortel; Martijs J. Jonker; Benno H. Ter Kuile
• Keywords: Kanamycin; Stringent response; SOS response; Gene knockout

Resistance evolution during exposure to non-lethal levels of antibiotics is influenced by various stress responses bacteria which are known affect growth rate. Here, we aim disentangle how the interplay between resistance development and associated fitness costs affected responses. We performed de novo wild-type strains single-gene knockout in response pathways using four different antibiotics. Throughout development, increase minimum inhibitory concentration (MIC) accompanied a gradual decrease rate, most pronounced with amoxicillin or kanamycin. By measuring biomass yield on glucose whole-genome sequences at intermediate final timepoints, identified two patterns correlation MIC First, E. coli reactive oxygen species (ROS) acquire faster mutations related antibiotic permeability pumping out occur earlier. This increases metabolic burden resistant bacteria. Second, ΔrelA strain has reduced (p)ppGpp synthesis, restricted its stringent response, leading diminished rates. The ROS-related mutagenesis vulnerabilities within that can possibly be targeted prevent resistance.