AUTHOR=Chen Bo-Chen , Lin Chang-Xin , Chen Ni-Pi , Gao Cheng-Xian , Zhao Ying-Jie , Qian Chao-Dong TITLE=Phenanthrene Antibiotic Targets Bacterial Membranes and Kills Staphylococcus aureus With a Low Propensity for Resistance Development JOURNAL=Frontiers in Microbiology VOLUME=Volume 9 - 2018 YEAR=2018 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01593 DOI=10.3389/fmicb.2018.01593 ISSN=1664-302X ABSTRACT=New classes of antibiotics with different mechanisms of action are urgently required for combating antimicrobial resistance. BP03, a dihydro-biphenanthrene with significant antibacterial activity, was recently isolated from the fibrous roots of Bletilla striata. Here, we report the further characterization of the antimicrobial potential and mode of action of BP03. The phenanthrene compound inhibited the growth of all tested clinical isolates of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA). The minimum inhibitory concentrations (MICs) of BP03 against these pathogens ranged from 2-8 μg/mL. Minimum bactericidal concentration (MBC) tests were conducted, and the results demonstrated that BP03 was bactericidal against S. aureus. This effect was confirmed by the time-kill assays. At bactericidal concentrations, BP03 caused loss of membrane potential in B. subtilis and S. aureus and disrupted the bacterial membrane integrity of the two strains. The spontaneous mutation frequency of S. aureus to BP03 was determined to be lower than 10-9. The selection and whole genome sequencing of the BP03-resistant mutants of S. aureus indicated that the development of BP03 resistance in S. aureus involves mutations in multi-genes. All these observations can be rationalized by the suggestion that membrane is a biological target of BP03.