Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non‐Biofilm Cultures, and Mycobacterium tuberculosis. Issue 49 (20th October 2015)

• Record Type: Journal Article
• Authors: Garrison, Aaron T.; Abouelhassan, Yasmeen; Kallifidas, Dimitris; Bai, Fang; Ukhanova, Maria; Mai, Volker; Jin, Shouguang; Luesch, Hendrik; Huigens, Robert W.
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 49(2015)
• Page Start: 14819
• Page End: 14823
• Publication Date: 2015-10-20
• Subjects: bacterial biofilms -- biofilm eradication -- halogenated phenazines -- marine antibiotics -- medicinal chemistry; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201508155
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Conventional antibiotics are ineffective against non‐replicating bacteria (for example, bacteria within biofilms). We report a series of halogenated phenazines (HP), inspired by marine antibiotic 1, that targets persistent bacteria. HP 14 demonstrated the most potent biofilm eradication activities to date against MRSA, MRSE, and VRE biofilms (MBEC=0.2–12.5 μM), as well as the effective killing of MRSA persister cells in non‐biofilm cultures. Frontline MRSA treatments, vancomycin and daptomycin, were unable to eradicate MRSA biofilms or non‐biofilm persisters alongside 14 . HP 13 displayed potent antibacterial activity against slow‐growing M. tuberculosis (MIC=3.13 μM), the leading cause of death by bacterial infection around the world. HP analogues effectively target persistent bacteria through a mechanism that is non‐toxic to mammalian cells and could have a significant impact on treatments for chronic bacterial infections. Abstract : Killing the quiet bacteria : Biofilms and quiescent persister cells are typically resistant to standard antibiotics, and contribute to many human infections. Halogenated phenazines based on a marine natural product are shown to be potent anti‐biofilm and anti‐persister cell compounds, while displaying very limited cytotoxicity in mammalian cells.