The synergistic antibacterial effects of α-mangostin and colistin on colistin-resistant Gram-negative bacteria.

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.