Phenanthrene Antibiotic Targets Bacterial Membranes and Kills With a Low Propensity for Resistance Development.

New classes of antibiotics with different mechanisms of action are urgently required for combating antimicrobial resistance. Blestriacin, a dihydro-biphenanthrene with significant antibacterial activity, was recently isolated from the fibrous roots of . Here, we report the further characterization of the antimicrobial potential and mode of action of blestriacin. The phenanthrene compound inhibited the growth of all tested clinical isolates of including methicillin-resistant (MRSA). The minimum inhibitory concentrations (MICs) of blestriacin against these pathogens ranged from 2 to 8 μg/mL. Minimum bactericidal concentration (MBC) tests were conducted, and the results demonstrated that blestriacin was bactericidal against . This effect was confirmed by the time-kill assays. At bactericidal concentrations, blestriacin caused loss of membrane potential in and and disrupted the bacterial membrane integrity of the two strains. The spontaneous mutation frequency of to blestriacin was determined to be lower than 10. The selection and whole genome sequencing of the blestriacin -resistant mutants of indicated that the development of blestriacin resistance in involves mutations in multi-genes. All these observations can be rationalized by the suggestion that membrane is a biological target of blestriacin.