Journal of global antimicrobial resistance · 2025
The synergistic antibacterial effects of α-mangostin and colistin on colistin-resistant Gram-negative bacteria.
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Ye Fan, Lv Xiaowei, Guo Wenhui, Hu Panjie, Wei Mengjie, Yang Yuhan, Zhou Tieli, Wu Qing
Аннотация
OBJECTIVE: Colistin (COL) remains a critical therapeutic agent for multidrug-resistant Gram-negative bacterial infections caused by pathogens. However, its clinical utility is increasingly constrained by escalating resistance rates and significant nephrotoxicity/neurotoxicity. In this study, we innovatively developed a combination therapy of COL with α-mangostin (α-M), a bioactive compound derived from mangosteen, and investigated its antibacterial mechanisms, thereby expanding the potential applications of natural products in addressing antimicrobial resistance.
METHODS: This study innovatively proposes the natural bioactive compound α-M as a potentiating adjuvant for COL. Through the establishment of a comprehensive evaluation system: The in vitro bactericidal effects were validated through checkerboard assays and time-kill curve analysis; a murine thigh infection model was developed for in vivo validation; crystal violet staining and scanning electron microscopy were combined to assess biofilm inhibition; and reactive oxygen species assays, propidium iodide uptake tests, and confocal laser scanning microscopy were utilized to elucidate the underlying mechanisms involving membrane integrity disruption and oxidative stress induction.
RESULTS: The results demonstrated that the α-M and COL combination exhibited potent bactericidal activity against COL-resistant Gram-negative bacteria (COL-R GNB), within 24 h, while effectively inhibiting biofilm formation.
CONCLUSIONS: α-M could overcome bacterial resistance in COL-R GNB by disrupting membrane permeability and integrity, ultimately leading to lethal accumulation of intracellular reactive oxygen species. These findings not only provide novel therapeutic insights for combating COL-R GNB but also establish a theoretical foundation for the application of natural products in antimicrobial resistance control.
METHODS: This study innovatively proposes the natural bioactive compound α-M as a potentiating adjuvant for COL. Through the establishment of a comprehensive evaluation system: The in vitro bactericidal effects were validated through checkerboard assays and time-kill curve analysis; a murine thigh infection model was developed for in vivo validation; crystal violet staining and scanning electron microscopy were combined to assess biofilm inhibition; and reactive oxygen species assays, propidium iodide uptake tests, and confocal laser scanning microscopy were utilized to elucidate the underlying mechanisms involving membrane integrity disruption and oxidative stress induction.
RESULTS: The results demonstrated that the α-M and COL combination exhibited potent bactericidal activity against COL-resistant Gram-negative bacteria (COL-R GNB), within 24 h, while effectively inhibiting biofilm formation.
CONCLUSIONS: α-M could overcome bacterial resistance in COL-R GNB by disrupting membrane permeability and integrity, ultimately leading to lethal accumulation of intracellular reactive oxygen species. These findings not only provide novel therapeutic insights for combating COL-R GNB but also establish a theoretical foundation for the application of natural products in antimicrobial resistance control.