Mutations in ArgS Arginine-tRNA Synthetase Confer Additional Antibiotic Tolerance Protection to Extended-Spectrum-β-Lactamase-Producing Burkholderia thailandensis

Highly conserved PenI-type class A β-lactamase in pathogenic members of Burkholderia species can evolve to extended-spectrum β-lactamase (ESBL), which exhibits hydrolytic activity toward third-generation cephalosporins, while losing its activity toward the original penicillin substrates. We describe three single-amino-acid-substitution mutations in the ArgS arginine-tRNA synthetase that confer extra antibiotic tolerance protection to ESBL-producing Burkholderia thailandensis. This pathway can be exploited to evade antibiotic tolerance induction in developing therapeutic measures against Burkholderia species, targeting their essential aminoacyl-tRNA synthetases.