Departamento de Biologia Molecular, Universidade Federal da Paraíba, João Pessoa (PB), Brazil.
Phytother Res. 2009 Oct;23(10):1367-70. doi: 10.1002/ptr.2695.
In an ongoing project to evaluate natural compounds isolated from plants from the Brazilian biodiversity as modulators of antibiotic resistance, kaempferol-3-O-beta-d-(6''-E-p-coumaroyl) glucopyranoside (tiliroside), isolated from Herissantia tiubae (Malvaceae) was investigated using the strain SA-1199B of Staphylococcus aureus, which overexpresses the norA gene encoding the NorA efflux protein which extrudes hydrophilic fluorquinolones and some biocides, such as benzalkonium chloride, cetrimide, acriflavine and ethidium bromide. The minimum inhibitory concentrations (MICs) of the antibiotics and biocides were determined by the microdilution assay in the absence and in the presence of sub-inhibitory concentration of tiliroside. Although tiliroside did not display relevant antibacterial activity (MIC = 256 microg/mL), it modulated the activity of antibiotics, i.e. in combination with antibiotics a reduction in the MIC was observed for norfloxacin (16-fold), ciprofloxacin (16-fold), lomefloxacin (four-fold) and ofloxacin (two-fold), and an impressive reduction in the MICs for the biocides (up to 128-fold). The results presented here represent the first report of a kaempferol glycoside as a putative efflux pump inhibitor in bacteria. The present finding indicates that H. tiubae (and broadly Malvaceae) could serve as a source of plant-derived natural products that modulate bacterial resistance, i.e. a source of potential adjuvants of antibiotics.
在一项评估从巴西生物多样性植物中分离的天然化合物作为抗生素耐药性调节剂的持续项目中，从 Herissantia tiubae（锦葵科）中分离出的山奈酚-3-O-β-D-（6''-E-对香豆酰）葡萄糖苷（tiliroside），使用金黄色葡萄球菌 SA-1199B 菌株进行了研究，该菌株过度表达了 norA 基因，该基因编码 NorA 外排蛋白，可排出亲水性氟喹诺酮类药物和一些生物杀灭剂，如苯扎氯铵、十六烷基三甲溴化铵、吖啶黄和溴化乙锭。通过微量稀释法在无和存在亚抑制浓度 tiliroside 的情况下测定抗生素和生物杀灭剂的最小抑菌浓度（MIC）。尽管 tiliroside 没有显示出相关的抗菌活性（MIC=256μg/mL），但它调节了抗生素的活性，即在与抗生素联合使用时，观察到诺氟沙星（16 倍）、环丙沙星（16 倍）、洛美沙星（4 倍）和氧氟沙星（2 倍）的 MIC 降低，以及生物杀灭剂的 MIC 显著降低（高达 128 倍）。这里呈现的结果代表了首次报道山奈酚糖苷作为细菌中潜在的外排泵抑制剂。目前的发现表明，H. tiubae（以及广义的锦葵科）可以作为植物来源的天然产物的来源，这些产物可以调节细菌的耐药性，即抗生素的潜在佐剂来源。
