Tintino Saulo R, Morais-Tintino Cícera D, Campina Fábia F, Pereira Raimundo L, Costa Maria do S, Braga Maria Flaviana B M, Limaverde Paulo W, Andrade Jacqueline C, Siqueira-Junior José P, Coutinho Henrique Douglas Melo, Balbino Valdir Q, Leal-Balbino Tereza C, Ribeiro-Filho Jaime, Quintans-Júnior Lucindo J
Laboratory of Microbiology and Molecular Biology (LMBM), Department of Biological Chemistry/CCBS/URCA, Brazil.
Laboratory of Microrganism Genetics (LGM), Department of Molecular Biology/CCEN/UFPB, Brazil.
EXCLI J. 2016 Apr 29;15:315-22. doi: 10.17179/excli2016-277. eCollection 2016.
Alpha-tocopherol is one the most abundant and biologically active isoforms of vitamin E. This compound is a potent antioxidant and one of most studied isoforms of vitamin E. Vitamin D3 (cholecalciferol) is an important nutrient for calcium homeostasis and bone health, that has also been recognized as a potent modulator of the immune response. Methicillin-resistant Staphylococcus aureus (MRSA) is the most important causative agent of both nosocomial and community-acquired infections. The aim of this study was to evaluate the inhibitory effect of alpha-tocopherol and cholecalciferol on both S. aureus and multidrug resistant S. aureus efflux pumps. The RN4220 strain has the plasmid pUL5054 that is the carrier of gene that encodes the macrolide resistance protein (an efflux pump) MsrA; the IS-58 strain possesses the TetK tetracycline efflux protein in its genome and the 1199B strain resists to hydrophilic fluoroquinolones via a NorA-mediated mechanism. The antibacterial activity was evaluated by determining the Minimal Inhibitory Concentration (MIC) and a possible inhibition of efflux pumps was associated to a reduction of the MIC. In this work we observed that in the presence of the treatments there was a decrease in the MIC for the RN4220 and IS-58 strains, suggesting that the substances presented an inhibitory effect on the efflux pumps of these strains. Significant efforts have been done to identify efflux pump inhibitors (EPIs) from natural sources and, therefore, the antibacterial properties of cholecalciferol and alpha-tocopherol might be attributed to a direct effect on the bacterial cell depending on their amphipathic structure.
α-生育酚是维生素E中含量最丰富且生物活性最强的异构体之一。这种化合物是一种强效抗氧化剂,也是研究最多的维生素E异构体之一。维生素D3(胆钙化醇)是维持钙稳态和骨骼健康的重要营养素,也被认为是免疫反应的强效调节剂。耐甲氧西林金黄色葡萄球菌(MRSA)是医院获得性感染和社区获得性感染最重要的病原体。本研究的目的是评估α-生育酚和胆钙化醇对金黄色葡萄球菌和多重耐药金黄色葡萄球菌外排泵的抑制作用。RN4220菌株具有质粒pUL5054,该质粒是编码大环内酯抗性蛋白(一种外排泵)MsrA的基因的载体;IS-58菌株在其基因组中含有TetK四环素外排蛋白,1199B菌株通过NorA介导的机制对亲水性氟喹诺酮耐药。通过测定最低抑菌浓度(MIC)评估抗菌活性,外排泵的可能抑制与MIC的降低相关。在这项工作中,我们观察到在处理存在的情况下,RN4220和IS-58菌株的MIC降低,表明这些物质对这些菌株的外排泵具有抑制作用。人们已经做出了巨大努力从天然来源中鉴定外排泵抑制剂(EPI),因此,胆钙化醇和α-生育酚的抗菌特性可能归因于它们的两亲结构对细菌细胞的直接作用。