Mechanism of synergy between epigallocatechin gallate and β-lactams against methicillin-resistant Staphylococcus aureus
Mechanism of synergy between epigallocatechin gallate and β-lactams against methicillin-resistant Staphylococcus aureus
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DOI：
10.1128/aac.45.6.1737-1742.2001
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发表时间：
2001-06-01
影响因子：
4.9
通讯作者：
Shimamura, T
中科院分区：
文献类型：
--
作者：
Zhao, WH;Hu, ZQ;Shimamura, T
与(-)-表没食子儿茶素没食子酸酯（EGCg）对大肠杆菌的mic值（大于800杯/ml）相比，EGCg对甲氧西林敏感和耐甲氧西林金黄色葡萄球菌（MSSA和MRSA）的mic值为100杯/ml或更低。此外，低于25 pg / mi的EGCg明显逆转了MRSA对所有类型的β -内酰胺类药物的高水平耐药，包括青霉素、氧苄西林、甲氧西林、氨苄西林和头孢氨苄，EGCg还诱导了MSSA对β -内酰胺类药物的超敏感，MSSA不表达mecA，编码青霉素结合蛋白2' （PBP2'）。在EGCg浓度为6.25、12.5或25 μ g / ml的情况下，β -内酰胺类药物对25株MRSA分离株的分离抑制浓度（FIC）指数在0.126 ~ 0.625之间，但EGCg与氨苄西林对E、coli没有协同作用，EGCg在很大程度上降低了MRSA和MSSA对高离子强度和低渗透压外大气的耐受性，表明其对细胞壁有损伤。与葡聚糖和脂多糖（来自S的肽聚糖）不同，金黄色葡萄球菌阻断了EGCg的抗菌活性以及EGCg与oxacillin的协同作用，表明EGCg与肽聚糖在细胞壁上直接结合。EGCg与dl -环丝氨酸tan细胞壁合成抑制剂（与PBP2无关）具有协同作用，但与蛋白质和核酸合成抑制剂具有可加性或无显著作用。通过逆转录pcr和半定量PBP2‘胶乳凝集实验证实，EGCg既不抑制PBP2’ mRNA的表达，也不抑制PBP2‘的产生，这表明协同作用与PBP2’的产生无关。总之，EGCg和β -内酰胺直接或间接攻击细胞壁上的肽聚糖。EGCg通过直接结合肽聚糖干扰细胞壁的完整性，从而协同β -内酰胺类抗MRSA的活性。
Compared to MICs (more than 800 mug/ml) of (-)-epigallocatechin gallate (EGCg) against Escherchia coli, MICs of EGCg against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) were 100 mug/ml or less. Furthermore, less than 25 pg EGCg per mi obviously reversed the high level resistance of MRSA to all types of tested beta -lactams, including benzylpenicillin, oxacillin, methicillin, ampicillin, and cephalexin, EGCg also induced a supersusceptibility to beta -lactams in MSSA which does not express mecA, encoding penicillin-binding protein 2' (PBP2'), The fractional inhibitory concentration (FIC) indices of the tested beta -lactams against 25 isolates of MRSA were from 0.126 to 0.625 in combination,vith 6.25, 12.5 or 25 mug of EGCg per ml. However, no synergism was observed between EGCg and ampicillin against E, coli, EGCg largely reduced the tolerance of MRSA and MSSA to high ionic strength and low osmotic pressure in their external atmosphere, indicating damage of the cell wall. Unlike dextran and lipopolysaccharide, peptidoglycan from S, aureus blocked both the antibacterial activity of EGCg and the synergism between EGCg and oxacillin, suggesting a direct binding of EGCg with peptidoglycan on the cell wall. EGCg showed a synergistic effect with DL-cycloserine tan inhibitor of cell wall synthesis unrelated to PBP2') but additive or indifferent effect with inhibitors of protein and nuclear acid synthesis. EGCg did not suppress either PBP2' mRNA expression or PBP2' production, as confirmed by reverse transcription-PCR and a semiquantitative PBP2' latex agglutination assay, indicating an irrelevance between the synergy and PBP2' production. In summary, both EGCg and beta -lactams directly or indirectly attack the same site, peptidoglycan on the cell wall. EGCg synergizes the activity of beta -lactams against MRSA owing to interference with the integrity of the cell wall through direct binding to peptidoglycan.