1月5日,国际著名杂志PloS One在线刊登了国外研究人员的最新研究成果“Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics,”文章中,作者揭示了一种鞣花酸对金黄色葡萄球菌生物膜的生成有明显的抑制作用。
众所周知,金黄色葡萄球菌是一种耐药性极强的致病菌,近日有证据显示,耐甲氧西林金黄色葡萄球菌可以引起社区获得性感染,金黄色葡萄球菌肠炎是金黄色葡萄球菌引起的,多因原发疾病长期用抗生素引起肠道菌群失调所致,抗生素敏感菌株受到抑制,耐药的金黄色葡萄球菌株趁机繁殖。金黄色葡萄球菌为侵袭性细菌,能产生毒素,对肠道破坏性大,所以金黄色葡萄球菌肠炎起病急,中毒症状严重,主要表现为呕吐、发热、腹泻。
对于金黄色葡萄球菌的耐药性,目前并没有有效的抗菌药物来治疗该菌感染引起的疾病,金葡菌产生耐药性有一部分原因是因为生物被膜的聚集和难以清除,生物被膜主要会导致慢性感染,因为生物被膜的感染所导致的疾病主要包括乳腺炎、中耳炎、心内膜炎以及骨髓炎等,据统计,在美国每年增加1700万因为生物被膜感染的病人,并且伴随55万人的死亡,目前这种在这种紧迫的情况下,我们急需开发出一种新的抗菌药物来抵抗生物被膜的感染,在临床上减轻病人的痛苦以及经济负担。
文章中,作者Mark S. Smeltzer表示,他们通过实验研究发现了鞣花酸及衍生物中的植物天然混合产物(220D-F2)可以在一定程度上抑制金黄色葡萄球菌的生物被膜的形成,于此同时,也增加了金葡菌对抗生素的敏感性,这种鞣花酸来自一种蔷薇科植物---榆叶黑莓,过去,榆叶黑莓被意大利南部人用来治疗皮肤或者软组织感染等疾病。
作者的研究数据表明,在一定浓度的220D-F2下,金黄色葡萄球菌的生物被膜的产量不仅明显下降了,而且也增加了该菌对不同类别抗生素(包括达托霉素、克林霉素、苯唑西林等)的敏感性,通过进行肾脏细胞和肝细胞实验,作者发现,在220D-F2的作用下, 金葡菌的细胞毒性也明显下降了。研究人员研究中的这种鞣花酸有可能成为下一个抵抗金黄色葡萄球菌的新的抗菌药物,这篇文章的研究为临床上提供了很多指导意义。(生物谷Bioon.com)
(T.Shen编译 如有问题请及时指正)
doi:10.1371/journal.pone.0028737
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Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics
Cassandra L. Quave1, Miriam Estévez-Carmona2,4, Cesar M. Compadre2, Gerren Hobby1, Howard Hendrickson2, Karen E. Beenken1, Mark S. Smeltzer1,3*
Background Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections. Methodology/Principal Findings This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50–200 µg/mL, which were well below the concentrations required to limit bacterial growth (530–1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects. Conclusions/Significance These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections.