Effects and mechanism of butylated hydroxytoluene in enhancing antibacterial ac-tivity of β-lactam antibiotics
10.16303/j.cnki.1005-4545.2025.08.20
- VernacularTitle:2,6-二叔丁基对甲酚增强β-内酰胺类抗生素抗菌活性的作用及机制
- Author:
Sangyu HU
1
;
Linlin DING
1
;
Wenhua GAO
1
;
Xuming DENG
1
Author Information
1. 吉林大学动物医学学院,吉林长春 130062
- Publication Type:Journal Article
- Keywords:
butylated hydroxytoluene;
amoxicillin;
β-lactam antibiotics;
methicillin-resistant Staph-ylococcus aureus
- From:
Chinese Journal of Veterinary Science
2025;45(8):1735-1743,1753
- CountryChina
- Language:Chinese
-
Abstract:
Using conventional broth microdilution assays,the synthetic phenolic antioxidant 2,6-di-tert-butyl-4-methylphenol(butylated hydroxytoluene,BHT)was screened for synergistic antimi-crobial activity with β-lactam antibiotics.Further validation through checkerboard assays,growth curve analysis,and time-kill curve experiments confirmed the synergistic effect of BHT and β-lac-tams against methicillin-resistant Staphylococcus aureus(MRSA)(FICI≤0.5).To elucidate the underlying mechanism of synergy,this study evaluated changes in membrane permeability and pro-ton transmembrane gradients-key factors in biofilm functionality-along with critical indicators of bacterial energy metabolism,including ATP levels and the NAD+/NADH ratio.The results dem-onstrated that BHT disrupts the proton motive force(PMF),impairs membrane potential,and perturbs bacterial energy homeostasis,thereby significantly enhancing the antibacterial efficacy ofβ-lactams.Furthermore,a murine pneumonia infection model was established to assess the in vivo therapeutic efficacy of BHT combined with amoxicillin.The combination therapy alleviated pulmo-nary tissue damage,reduced bacterial loads in target organs(liver,spleen,and lungs),and decreased systemic inflammatory responses.This study elucidates the synergistic antimicrobial action and mechanistic basis of BHT combined with amoxicillin,offering a novel combinatorial therapeutic strategy to address MRSA resistance.The findings hold significant clinical potential and research value for overcoming antibiotic resistance in MRSA infections.
