Mutations in and Correlate with Quinolone Resistance in Wastewater .

Single mutations can confer resistance to antibiotics. Identifying such mutations can help to develop and improve drugs. Here, we systematically screen for candidate quinolone resistance-conferring mutations. We sequenced highly diverse wastewater and performed a genome-wide association study (GWAS) to determine associations between over 200,000 mutations and quinolone resistance phenotypes. We uncovered 13 statistically significant mutations including 1 located at the active site of the biofilm dispersal gene and 6 silent mutations in the aminoacyl-tRNA synthetase . The study also recovered the known mutations in the topoisomerases gyrase () and topoisomerase IV (). In summary, we demonstrate that GWAS effectively and comprehensively identifies resistance mutations without a priori knowledge of targets and mode of action. The results suggest that mutations in the and genes, which are involved in biofilm dispersal and translation, may lead to novel resistance mechanisms.