Work

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

Year: 2025

Type: article

Abstract: • Synergistic Plant-Antibiotic Innovation: • First study combining α-Mangostin with colistin to boost efficacy and combat resistance, advancing natural product applications against drug-resistant infections. • Multifaceted Resistance Reversal: • α-Mangostin disrupts membranes, compromises integrity, and induces lethal reactive oxygen species, elucidating colistin resistance reversal. • Biofilm Inhibition Breakthrough: • The combo effectively suppresses biofilm formation, offering novel treatment for chronic and device-related infections. 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. 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. The results demonstrated that the α-M and COL combination exhibited potent bactericidal activity against colistin-resistant gram-negative bacteria (COL-R GNB), within 24 hours while effectively inhibiting biofilm formation. 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.

Source: Journal of Global Antimicrobial Resistance

DOI: 10.1016/j.jgar.2025.10.018