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Photo-Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA.

Authors
  • Hui, Jie1, 2
  • Dong, Pu-Ting2, 3
  • Liang, Lijia1, 4
  • Mandal, Taraknath3
  • Li, Junjie1, 2
  • Ulloa, Erlinda R5, 6
  • Zhan, Yuewei7
  • Jusuf, Sebastian7
  • Zong, Cheng1, 2
  • Seleem, Mohamed N8
  • Liu, George Y5, 9
  • Cui, Qiang3, 7
  • Cheng, Ji-Xin1, 2, 3, 7
  • 1 Department of Electrical and Computer Engineering Boston University Boston MA 02215 USA.
  • 2 Boston University Photonics Center Boston MA 02215 USA.
  • 3 Department of Chemistry Boston University Boston MA 02215 USA.
  • 4 State Key Laboratory of Supramolecular Structure and Materials Institute of Theoretical Chemistry Jilin University Changchun 130012 China. , (China)
  • 5 Collaborative to Halt Antibiotic-Resistant Microbes (CHARM) Department of Pediatrics University of California San Diego School of Medicine La Jolla CA 92093 USA.
  • 6 Division of Infectious Disease Department of Pediatrics Children's Hospital of Philadelphia Philadelphia PA 19104 USA.
  • 7 Department Biomedical Engineering Boston University Boston MA 02215 USA.
  • 8 College of Veterinary Medicine Purdue University West Lafayette IN 47907 USA.
  • 9 Division of Infectious Diseases Rady Children's Hospital San Diego CA 92123 USA.
Type
Published Article
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Publication Date
Mar 01, 2020
Volume
7
Issue
6
Pages
1903117–1903117
Identifiers
DOI: 10.1002/advs.201903117
PMID: 32195102
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

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