A new therapeutic strategy for infectious diseases against intracellular multidrug-resistant bacteria.
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| Title: | A new therapeutic strategy for infectious diseases against intracellular multidrug-resistant bacteria. |
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| Authors: | Wang, Zhao-Jie1 (AUTHOR), Zhu, Yan-Yan1 (AUTHOR), Bai, Li-Yu1 (AUTHOR), Tang, Dong-Mei1 (AUTHOR), Zhou, Zhong-Shun1 (AUTHOR), Wei, Mei-Zhen1 (AUTHOR), He, Jin-Biao1 (AUTHOR), Yu-Duan1 (AUTHOR), Luo, Xiao-Dong1,2 (AUTHOR) xdluo@ynu.edu.cn |
| Source: | Journal of Controlled Release. Nov2024, Vol. 375, p467-477. 11p. |
| Subjects: | Methicillin-resistant staphylococcus aureus, Protein synthesis, Bacterial diseases, Enterococcus, Communicable diseases |
| Abstract: | Bacterial infections result in 7,700,000 deaths per year globally, with intracellular bacteria causing repeated and resistant infection. No drug is currently licenced for the treatment of intracellular bacteria. A new screening platform mimicking the host milieu has been established to explore phytochemical antibiotic adjuvants. Previously neglected isoprenylated flavonoids were found to be effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Specifically, the synergistic effect between glabrol and streptomycin against intracellular bacteria was observed for the first time. The glabrol-streptomycin combination targets bacterial inner membrane phospholipids, disrupts arginine biosynthesis, inhibits cell wall proteins and biofilm formation genes (agrA/B/C/D), and promotes ROS production, causing subsequent membrane and wall damage. To enhance the selective uptake of combination drug into infected cells, hyaluronic acid-streptomycin-lipoic acid-glabrol nanoparticles (HSLGS-S) were designed and synthesized to trigger the intracellular delivery of the glabrol-streptomycin combination. Thus, the treatment can be transported into the infected intracellular region and selectively release the glabrol-streptomycin combination to the bacterial at site. The bioactivity of HSLGS-S in clearing intracellular bacteria was 20-fold higher than that of the glabrol-streptomycin combination alone in vitro and 2- to 10-fold higher in vivo. [Display omitted] • A new screening platform to explore antibiotic adjuvants with the previously neglected phytochemicals. • Glabrol-streptomycin destroyed bacterial inner membrane, arginine biosynthesis, the cell wall proteins and biofilm formation. • HSLGS-S against intracellular MDR bacteria in vivo and in vitro. [ABSTRACT FROM AUTHOR] |
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| Database: | Engineering Source |
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