Open AccessPhoto‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA
Author(s) -
Hui Jie,
Dong PuTing,
Liang Lijia,
Mandal Taraknath,
Li Junjie,
Ulloa Erlinda R.,
Zhan Yuewei,
Jusuf Sebastian,
Zong Cheng,
Seleem Mohamed N.,
Liu George Y.,
Cui Qiang,
Cheng JiXin
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201903117
Subject(s) - antibiotics , phototoxicity , microbiology and biotechnology , membrane , antibiotic resistance , chemistry , in vivo , biology , in vitro , biochemistry
Confronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug‐resistant pathogens. Here, an unconventional approach is presented to restore the susceptibility of methicillin‐resistant S. aureus (MRSA) to a broad spectrum of conventional antibiotics via photo‐disassembly of functional membrane microdomains. The photo‐disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name. Upon pulsed laser treatment, cell membranes are found severely disorganized and malfunctioned to defense antibiotics, as unveiled by membrane permeabilization, membrane fluidification, and detachment of membrane protein, PBP2a. Consequently, the photolysis approach increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglycosides, lipopeptides, and oxazolidinones. The synergistic therapy, without phototoxicity to the host, is effective in combating MRSA both in vitro and in vivo in a mice skin infection model. Collectively, this endogenous chromophore‐targeted phototherapy concept paves a novel platform to revive conventional antibiotics to combat drug‐resistant S. aureus infections as well as to screen new lead compounds.