Department of Biological Chemistry, URCA, Crato, Brazil.
Department of Molecular Biology, UFPB, Joao Pessoa, Brazil.
Curr Drug Metab. 2021;22(2):123-126. doi: 10.2174/1389200221999200730212721.
Infectious diseases have been responsible for an increasing number of deaths worldwide. Staphylococcus aureus has been recognized as one of the most notable causative agents of severe infections, while efflux pump (EP) expression is one of the main mechanisms associated with S. aureus resistance to antibiotics.
This study aimed to investigate the potential of α-pinene as an efflux pump inhibitor in species of S. aureus carrying the TetK and MrsA proteins.
The minimum inhibitory concentrations (MIC) of α-pinene and other efflux pump inhibitors were assessed using serial dilutions of each compound at an initial concentration above 1024 μg/mL. Solutions containing culture medium and bacterial inoculums were prepared in test tubes and subsequently transferred to 96-well microdilution plates. The modulation of ethidium bromide (EtBr) and antibiotics (tetracycline and erythromycin) was investigated through analysis of the modification in their MICs in the presence of a subinhibitory concentration of α-pinene (MIC/8). Wells containing only culture medium and bacterial inoculums were used as negative control. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) was used as a positive control.
The MIC of ethidium bromide against S. aureus strains RN-4220 and IS-58 was reduced by association with α-pinene. This monoterpene potentiated the effect of tetracycline against the IS-58 strain but failed in modulating the antibacterial effect of erythromycin against RN-4220, suggesting a selective inhibitory effect on the TetK EP by α- pinene.
In conclusion, α-pinene has promising effects against S.aureus strains, which should be useful in the combat of antibacterial resistance associated with EP expression. Nevertheless, further research is required to fully characterize its molecular mechanism of action as an EP inhibitor.
传染病在全球范围内导致的死亡人数不断增加。金黄色葡萄球菌已被认为是引起严重感染的主要病原体之一，而外排泵（EP）表达是与金黄色葡萄球菌对抗生素耐药性相关的主要机制之一。
本研究旨在探讨 α-蒎烯作为携带 TetK 和 MrsA 蛋白的金黄色葡萄球菌种属外排泵抑制剂的潜力。
采用初始浓度高于 1024 μg/mL 的各化合物连续稀释法评估 α-蒎烯和其他外排泵抑制剂的最小抑菌浓度（MIC）。在试管中制备含有培养基和细菌接种物的溶液，然后将其转移到 96 孔微稀释板中。通过分析亚抑菌浓度 α-蒎烯（MIC/8）存在时溴化乙锭（EtBr）和抗生素（四环素和红霉素）的 MIC 变化来研究其调制作用。仅含有培养基和细菌接种物的孔作为阴性对照。羰基氰化物 m-氯苯腙（CCCP）用作阳性对照。
与 α-蒎烯联合使用时，金黄色葡萄球菌 RN-4220 和 IS-58 菌株的溴化乙锭 MIC 降低。这种单萜类化合物增强了 IS-58 株对四环素的作用，但未能调节 RN-4220 对抗生素红霉素的抗菌作用，表明 α-蒎烯对 TetK EP 具有选择性抑制作用。
总之，α-蒎烯对金黄色葡萄球菌菌株具有良好的效果，这对于对抗与 EP 表达相关的抗菌耐药性可能非常有用。然而，需要进一步研究以充分表征其作为 EP 抑制剂的分子作用机制。
