在长期的抗生素选择之后出现的对相应抗生素产生耐受能力的微生物，统称耐药菌。所谓细菌的耐药性，是指细菌多次与药物接触后，对药物的敏感性减小甚至消失，致使药物对耐药菌的疗效降低甚至无效。耐药菌的出现增加了感染性疾病治愈的难度，并迫使人类寻找新的对抗微生物感染的方法。
金黄色葡萄球菌是伤口感染的最常见细菌，自1940年以来金黄色葡萄球菌感染已经是世界各地医院头疼的问题之一，金黄色葡萄球菌是已知的抗药性最多的细菌。
近来，丹麦哥本哈根大学的科学家在J Antimicrob Chemother上发表文章称：他们在智利热带雨林植物中发现了一种天然物质，该物质能有效加强传统抗生素治疗的效果。
哥本哈根大学Jes-Gitz-Holler博士在智利鳄梨植物中发现了一种天然化合物，该物质对出现耐药性的金黄色葡萄球菌有抑制作用，与传统的抗生素联合运用的话能起到协同增效的功能。
耐药性细菌细胞膜上通常存在一高效泵，一旦外抗生素进入细菌后，泵能及时向外排出抗生素。而新发现的天然物质恰巧可以抑制细菌泵的功能，抑制抗生素向外排出，使细菌的耐药防御机制受到破坏。
目前，市场上并没有类似的抑制抗生素外排的药品，所以新发现的化合物很有可能成为治疗金黄色葡萄球菌感染的有效药物。但出于保护热带雨林植物，Jes-Gitz-Holler博士强调我们必须要能够在实验室里合成这一化学物质。（生物谷Bioon.com）
doi:10.1093/jac/dks005
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Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees
Jes Gitz Holler1,*,S. Brgger Christensen1,Hans-Christian Slotved2,Hasse B. Rasmussen1,Alfonso Gúzman1,Carl-Erik Olsen3,Bent Petersen4 and Per Mlgaard1
Objectives To isolate a plant-derived compound with efflux inhibitory activity towards the NorA transporter of Staphylococcus aureus.
Methods Bioassay-guided isolation was used, with inhibition of ethidium bromide efflux via NorA as a guide. Characterization of activity was carried out using MIC determination and potentiation studies of a fluoroquinolone antibiotic in combination with the isolated compound. Everted membrane vesicles of Escherichia coli cells enriched with NorA were prepared to study efflux inhibitory activity in an isolated manner.
Results The ethanolic extract of Persea lingue was subjected to bioassay-guided fractionation and led to the isolation of the known compound kaempferol-3-O-α-l-(2,4-bis-E-p-coumaroyl)rhamnoside (compound 1). Evaluation of the dose–response relationship of compound 1 showed that ethidium bromide efflux was inhibited, with an IC50 value of 2 μM. The positive control, reserpine, was found to have an IC50 value of 9 μM. Compound 1 also inhibited NorA in enriched everted membrane vesicles of E. coli. Potentiation studies revealed that compound 1 at 1.56 mg/L synergistically increased the antimicrobial activity of ciprofloxacin 8-fold against a NorA overexpresser, and the synergistic activity was exerted at a fourth of the concentration necessary for reserpine. Compound 1 was not found to exert a synergistic effect on ciprofloxacin against a norA deletion mutant. The 2,3-coumaroyl isomer of compound 1 has been shown previously not to cause acute toxicity in mice at 20 mg/kg/day.
Conclusions Our results show that compound 1 acts through inhibition of the NorA efflux pump. Combination of compound 1 with subinhibitory concentrations of ciprofloxacin renders a wild-type more susceptible and a NorA overexpresser S. aureus susceptible.
