Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA

Advanced Science

Pu‐Ting Dong¹  George Y. Liu²  Erlinda R. Ulloa²  Mohamed N. Seleem³  Yuewei Zhan⁴  Sebastian Jusuf⁴  Taraknath Mandal⁵  Qiang Cui⁵  Ji‐Xin Cheng⁶  Lijia Liang⁶  Cheng Zong⁶  Junjie Li⁶  Jie Hui⁶ 

[1] Boston University Photonics Center Boston MA 02215 USA;Collaborative to Halt Antibiotic‐Resistant Microbes (CHARM) Department of Pediatrics University of California San Diego School of Medicine La Jolla CA 92093 USA;College of Veterinary Medicine Purdue University West Lafayette IN 47907 USA;Department Biomedical Engineering Boston University Boston MA 02215 USA;Department of Chemistry Boston University Boston MA 02215 USA;Department of Electrical and Computer Engineering Boston University Boston MA 02215 USA;

关键词: antibiotic resistance;    membrane microdomains;    pulsed lasers;    Staphylococcus aureus;    staphyloxanthin;   

DOI  :  10.1002/advs.201903117

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown