Genetic characterization of spontaneous resistance mutations for gepotidacin against a collection of Gram-Positive and Gram-Negative organisms

Select colonies demonstrating reduced gepotidacin susceptibility underwent whole genome sequencing and comparative genomics to identify potential mechanisms of resistance. Resistant mutants and their respective parental isolates were sequenced using a combination of short- and long-read sequencing methods. For single nucleotide polymorphism (SNP) analysis, short- and long-reads were assembled and SNPs confirmed by mapping quality trimmed reads independently to the baseline assembly. These results show that the most common SNPs observed conferring less susceptibility to gepotidacin among Gram-negative isolates coalesced around the potential contributions of overexpressed efflux pumps derived from repressor inactivation or activator dysregulation.