Pterostilbene synergizes with colistin against multidrug-resistant bacteria via iron chelation and membrane disruption, and promotes gut health restoration in weaned piglets.

Pterostilbene restores colistin efficacy against resistant bacteria and improves gut health in piglets.

This study demonstrates that pterostilbene (PTE), a natural phenolic compound from blueberries and grapes, synergistically enhances colistin efficacy against multidrug-resistant Gram-negative bacteria. The mechanism involves iron chelation that disrupts bacterial iron homeostasis, compromises outer membrane integrity, and increases inner membrane phospholipid susceptibility. When combined with colistin, PTE induces a futile metabolic cycle causing severe ATP depletion and leakage. The combination effectively eliminates persister cells and suppresses biofilm formation. In vivo efficacy was demonstrated in a Galleria mellonella infection model with improved survival rates. Notably, in weaned piglets, PTE supplementation promoted restoration of balanced gut microbiota while reducing pathogenic bacteria. This represents a novel, food-compatible adjuvant strategy to resensitize resistant bacteria to polymyxin therapy, offering a sustainable approach for controlling resistant infections in food-animal production systems while maintaining gut health and supporting natural microbial balance.

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