2. Academic Validation
  3. The Synergistic Antibacterial Effects of α-Mangostin and Colistin on Colistin-Resistant Gram-Negative Bacteria

The Synergistic Antibacterial Effects of α-Mangostin and Colistin on Colistin-Resistant Gram-Negative Bacteria

  • J Glob Antimicrob Resist. 2025 Oct 29:S2213-7165(25)00236-X. doi: 10.1016/j.jgar.2025.10.018.
Fan Ye 1,  Xiaowei Lv 1,  Wenhui Guo 1,  Panjie Hu 1,  Mengjie Wei 1,  Yuhan Yang 2,  Tieli Zhou 3,  Qing Wu 4
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang Province, 325035, China.
  • 2 School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, China.
  • 3 Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang Province, 325035, China. Electronic address: wyztli@163.com.
  • 4 Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang Province, 325035, China. Electronic address: wuqing830@163.com.
PMID: 41173103 DOI: 10.1016/j.jgar.2025.10.018
Abstract

Objectives: 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 colistin-resistant gram-negative bacteria (COL-R GNB), within 24 hours 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.

Keywords

Gram-negative bacteria; biofilm; colistin resistance; synergistic; α-Mangostin.

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