Centro de Ciências Agrárias e Ambientais, Universidade Federal do Maranhão, Campus Chapadinha S/N, Chapadinha, Maranhão, 65500-000, Brazil.
Departamento de Química Biológica, Universidade Regional do Cariri, Crato, Ceará, Brazil.
Probiotics Antimicrob Proteins. 2020 Mar;12(1):82-90. doi: 10.1007/s12602-019-9526-z.
The use of natural products together with standard antimicrobial drugs has recently received more attention as a strategy to combat infectious diseases caused by multidrug-resistant (MDR) microorganisms. This study aimed to evaluate the capacity of a galactose-binding lectin from Vatairea macrocarpa seeds (VML) to modulate antibiotic activity against standard and MDR Staphylococcus aureus and Escherichia coli bacterial strains. The minimum inhibitory concentration (MIC) obtained for VML against all strains was not clinically relevant (MIC ≥ 1024 μg/mL). However, when VML was combined with the antibacterial drugs gentamicin, norfloxacin and penicillin, a significant increase in antibiotic activity was observed against S. aureus, whereas the combination of VML and norfloxacin presented decreased and, hence, antagonistic antibiotic activity against E. coli. By its inhibition of hemagglutinating activity, gentamicin (MIC = 50 mM) revealed its interaction with the carbohydrate-binding site (CBS) of VML. Using molecular docking, it was found that gentamicin interacts with residues that constitute the CBS of VML with a score of - 120.79 MDS. It is this interaction between the antibiotic and the lectin's CBS that may be responsible for the enhanced activity of gentamicin in S. aureus. Thus, our results suggest that the VML can be an effective modulating agent against S. aureus. This is the first study to report the effect of lectins as modulators of bacterial sensitivity, and as such, the outcome of this study could lay the groundwork for future research involving the use of lectins and conventional antibiotics against such infectious diseases such as community-acquired methicillin-resistant S. aureus (MRSA).
天然产物与标准抗菌药物联合使用最近受到了更多关注,成为对抗多药耐药(MDR)微生物引起的感染性疾病的一种策略。本研究旨在评估来自 Vatairea macrocarpa 种子的半乳糖结合凝集素(VML)调节抗生素活性对抗标准和 MDR 金黄色葡萄球菌和大肠杆菌菌株的能力。VML 对所有菌株的最低抑菌浓度(MIC)没有临床意义(MIC≥1024μg/mL)。然而,当 VML 与抗菌药物庆大霉素、诺氟沙星和青霉素联合使用时,观察到对金黄色葡萄球菌的抗生素活性显著增加,而 VML 与诺氟沙星的组合对大肠杆菌表现出降低的、因此是拮抗的抗生素活性。通过抑制血凝活性,庆大霉素(MIC=50mM)揭示了其与 VML 的碳水化合物结合位点(CBS)的相互作用。通过分子对接,发现庆大霉素与构成 VML CBS 的残基相互作用,得分为-120.79 MDS。正是抗生素和凝集素 CBS 之间的这种相互作用可能是庆大霉素在金黄色葡萄球菌中活性增强的原因。因此,我们的研究结果表明,VML 可以作为对抗金黄色葡萄球菌的有效调节剂。这是首次报道凝集素作为细菌敏感性调节剂的作用的研究,因此,这项研究的结果可为未来使用凝集素和传统抗生素对抗社区获得性耐甲氧西林金黄色葡萄球菌(MRSA)等传染病的研究奠定基础。