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Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non‐Biofilm Cultures, and Mycobacterium tuberculosis
Author(s) -
Garrison Aaron T.,
Abouelhassan Yasmeen,
Kallifidas Dimitris,
Bai Fang,
Ukhanova Maria,
Mai Volker,
Jin Shouguang,
Luesch Hendrik,
Huigens Robert W.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201508155
Subject(s) - biofilm , multidrug tolerance , microbiology and biotechnology , daptomycin , bacteria , antibiotics , mycobacterium tuberculosis , staphylococcus aureus , methicillin resistant staphylococcus aureus , vancomycin , biology , tuberculosis , medicine , genetics , pathology
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.