Angucyclinones rescue PhLOPSA antibiotic activity by inhibiting Cfr-dependent antibiotic resistance

IMPORTANCE: Cfr is an antibiotic resistance enzyme that inhibits five clinically important antibiotic classes, is genetically mobile, and has a minimal fitness cost, making Cfr a serious threat to antibiotic efficacy. The significance of our work is in discovering molecules that inhibit Cfr-dependent methylation of the ribosome, thus protecting the efficacy of the PhLOPS_A antibiotics. These molecules are the first reported inhibitors of …