Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA
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 (M...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.201903117 |
| _version_ | 1818901986402107392 |
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| author | Jie Hui Pu‐Ting Dong Lijia Liang Taraknath Mandal Junjie Li Erlinda R. Ulloa Yuewei Zhan Sebastian Jusuf Cheng Zong Mohamed N. Seleem George Y. Liu Qiang Cui Ji‐Xin Cheng |
| author_facet | Jie Hui Pu‐Ting Dong Lijia Liang Taraknath Mandal Junjie Li Erlinda R. Ulloa Yuewei Zhan Sebastian Jusuf Cheng Zong Mohamed N. Seleem George Y. Liu Qiang Cui Ji‐Xin Cheng |
| author_sort | Jie Hui |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T20:28:28Z |
| format | Article |
| id | doaj.art-dbcd162e93024c129ffe703948da2d75 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-19T20:28:28Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-dbcd162e93024c129ffe703948da2d752022-12-21T20:06:47ZengWileyAdvanced Science2198-38442020-03-0176n/an/a10.1002/advs.201903117Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSAJie Hui0Pu‐Ting Dong1Lijia Liang2Taraknath Mandal3Junjie Li4Erlinda R. Ulloa5Yuewei Zhan6Sebastian Jusuf7Cheng Zong8Mohamed N. Seleem9George Y. Liu10Qiang Cui11Ji‐Xin Cheng12Department of Electrical and Computer Engineering Boston University Boston MA 02215 USABoston University Photonics Center Boston MA 02215 USADepartment of Electrical and Computer Engineering Boston University Boston MA 02215 USADepartment of Chemistry Boston University Boston MA 02215 USADepartment of Electrical and Computer Engineering Boston University Boston MA 02215 USACollaborative to Halt Antibiotic‐Resistant Microbes (CHARM) Department of Pediatrics University of California San Diego School of Medicine La Jolla CA 92093 USADepartment Biomedical Engineering Boston University Boston MA 02215 USADepartment Biomedical Engineering Boston University Boston MA 02215 USADepartment of Electrical and Computer Engineering Boston University Boston MA 02215 USACollege of Veterinary Medicine Purdue University West Lafayette IN 47907 USACollaborative to Halt Antibiotic‐Resistant Microbes (CHARM) Department of Pediatrics University of California San Diego School of Medicine La Jolla CA 92093 USADepartment of Chemistry Boston University Boston MA 02215 USADepartment of Electrical and Computer Engineering Boston University Boston MA 02215 USAAbstract 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.https://doi.org/10.1002/advs.201903117antibiotic resistancemembrane microdomainspulsed lasersStaphylococcus aureusstaphyloxanthin |
| spellingShingle | Jie Hui Pu‐Ting Dong Lijia Liang Taraknath Mandal Junjie Li Erlinda R. Ulloa Yuewei Zhan Sebastian Jusuf Cheng Zong Mohamed N. Seleem George Y. Liu Qiang Cui Ji‐Xin Cheng Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA Advanced Science antibiotic resistance membrane microdomains pulsed lasers Staphylococcus aureus staphyloxanthin |
| title | Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA |
| title_full | Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA |
| title_fullStr | Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA |
| title_full_unstemmed | Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA |
| title_short | Photo‐Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA |
| title_sort | photo disassembly of membrane microdomains revives conventional antibiotics against mrsa |
| topic | antibiotic resistance membrane microdomains pulsed lasers Staphylococcus aureus staphyloxanthin |
| url | https://doi.org/10.1002/advs.201903117 |
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