Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus

Xiaohong Yang, Gongming Shi, Jian Guo, Chenhui Wang, Yun He Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People’s Republic of China Background: Staphylococcus aureus survival inside pha...

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Autores principales: Yang X, Shi G, Guo J, Wang C, He Y
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Publicado: Dove Medical Press 2018
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spelling oai:doaj.org-article:8ec8a5a2db9d41ccad70245a71cafa072021-12-02T09:50:43ZExosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus1178-2013https://doaj.org/article/8ec8a5a2db9d41ccad70245a71cafa072018-11-01T00:00:00Zhttps://www.dovepress.com/exosome-encapsulated-antibiotic-against-intracellular-infections-of-me-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaohong Yang, Gongming Shi, Jian Guo, Chenhui Wang, Yun He Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People’s Republic of China Background: Staphylococcus aureus survival inside phagocytes is considered to provide a reservoir of bacteria that are relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Purpose: The objective of this study was to develop a nanovesicle using exosomes loaded with linezolid to overcome intracellular infections by pathogenic bacteria. Methods: Exosomes were collected from the culture supernatants of RAW 264.7 cells. Their size distribution and zeta potential were characterized by dynamic light scattering, their morphology was characterized by transmission electron microscopy, and their protein content (CD63 and Flotillin 1) was assessed by Western blotting. Linezolid was incorporated into exosomes by co-incubation at 37°C and it’s accumulation in RAW264.7 cells and release in vitro were determined by high performance liquid chromatography. The intracellular bactericidal effect was evaluated in methicillin-resistant S. aureus (MRSA)-infected macrophages in vitro and MRSA peritonitis model in vivo. Results: We prepared a nanoformulation of the antibiotic linezolid using exosomes harvested from mouse RAW264.7 macrophages. The exosomal formulation of linezolid was more effective against intracellular MRSA infections in vitro and in vivo than the free linezolid. Our data also showed no signs of cytotoxicity in macrophages. Conclusion: Exosomes provide an effective alternative for intracellular antibiotic delivery of antibiotic that is efficacious, cost-effective, and safe. This regimen can be viewed as a potential antimicrobial agent for use against intracellular infections. Keywords: exosomes, antibiotic, delivery, intracellular infection, MRSAYang XShi GGuo JWang CHe YDove Medical PressarticleExosomesAntibioticDeliveryIntracellular infectionMRSAMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 8095-8104 (2018)
institution DOAJ
collection DOAJ
language EN
topic Exosomes
Antibiotic
Delivery
Intracellular infection
MRSA
Medicine (General)
R5-920
spellingShingle Exosomes
Antibiotic
Delivery
Intracellular infection
MRSA
Medicine (General)
R5-920
Yang X
Shi G
Guo J
Wang C
He Y
Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus
description Xiaohong Yang, Gongming Shi, Jian Guo, Chenhui Wang, Yun He Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, People’s Republic of China Background: Staphylococcus aureus survival inside phagocytes is considered to provide a reservoir of bacteria that are relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Purpose: The objective of this study was to develop a nanovesicle using exosomes loaded with linezolid to overcome intracellular infections by pathogenic bacteria. Methods: Exosomes were collected from the culture supernatants of RAW 264.7 cells. Their size distribution and zeta potential were characterized by dynamic light scattering, their morphology was characterized by transmission electron microscopy, and their protein content (CD63 and Flotillin 1) was assessed by Western blotting. Linezolid was incorporated into exosomes by co-incubation at 37°C and it’s accumulation in RAW264.7 cells and release in vitro were determined by high performance liquid chromatography. The intracellular bactericidal effect was evaluated in methicillin-resistant S. aureus (MRSA)-infected macrophages in vitro and MRSA peritonitis model in vivo. Results: We prepared a nanoformulation of the antibiotic linezolid using exosomes harvested from mouse RAW264.7 macrophages. The exosomal formulation of linezolid was more effective against intracellular MRSA infections in vitro and in vivo than the free linezolid. Our data also showed no signs of cytotoxicity in macrophages. Conclusion: Exosomes provide an effective alternative for intracellular antibiotic delivery of antibiotic that is efficacious, cost-effective, and safe. This regimen can be viewed as a potential antimicrobial agent for use against intracellular infections. Keywords: exosomes, antibiotic, delivery, intracellular infection, MRSA
format article
author Yang X
Shi G
Guo J
Wang C
He Y
author_facet Yang X
Shi G
Guo J
Wang C
He Y
author_sort Yang X
title Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus
title_short Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus
title_full Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus
title_fullStr Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus
title_full_unstemmed Exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant Staphylococcus aureus
title_sort exosome-encapsulated antibiotic against intracellular infections of methicillin-resistant staphylococcus aureus
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/8ec8a5a2db9d41ccad70245a71cafa07
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AT shig exosomeencapsulatedantibioticagainstintracellularinfectionsofmethicillinresistantstaphylococcusaureus
AT guoj exosomeencapsulatedantibioticagainstintracellularinfectionsofmethicillinresistantstaphylococcusaureus
AT wangc exosomeencapsulatedantibioticagainstintracellularinfectionsofmethicillinresistantstaphylococcusaureus
AT hey exosomeencapsulatedantibioticagainstintracellularinfectionsofmethicillinresistantstaphylococcusaureus
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