Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant Staphylococci
Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant Staphylococci
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DOI：
10.1038/ja.2014.142
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发表时间：
2015-04-01
影响因子：
3.3
通讯作者：
Seleem, Mohamed N.
中科院分区：
文献类型：
--
作者：
Mohammad, Haroon;Mayhoub, Abdelrahman S.;Seleem, Mohamed N.
耐甲氧西林金黄色葡萄球菌（MRSA）感染是由耐甲氧西林细菌引起的所有死亡中的主要死因。随着对当前抗生素耐药性的增强，迫切需要新的抗菌药物和治疗策略。噻唑化合物已被证明具有有效的抗微生物活性。合成了一个噻唑先导化合物1和一个有效的衍生物2，并测定了它们与糖肽类抗生素组合对一系列MRSA和万古霉素耐药的S.金黄色葡萄球菌（VRSA）临床分离株。此外，研究了新噻唑类化合物对沙门氏菌的抗生物膜活性。表皮化合物2与万古霉素对MRSA表现出协同作用，并且能够使VRSA对万古霉素重新敏感，在两种菌株中将其MIC降低512倍。此外，两种噻唑化合物在显著降低S.表皮生物膜团块。总的来说，所获得的结果表明，化合物1和2单独或与万古霉素组合对多重耐药葡萄球菌具有有效的抗微生物活性，并显示出用于破坏葡萄球菌生物膜的潜力。
Methicillin-resistant Staphylococcus aureus (MRSA) infections are a leading cause of death among all fatalities caused by antibiotic-resistant bacteria. With the rise of increasing resistance to current antibiotics, new antimicrobials and treatment strategies are urgently needed. Thiazole compounds have been shown to possess potent antimicrobial activity. A lead thiazole 1 and a potent derivative 2 were synthesized and their activity in combination with glycopeptide antibiotics was determined against an array of MRSA and vancomycin-resistant S. aureus (VRSA) clinical isolates. In addition, the anti-biofilm activity of the novel thiazoles was investigated against S. epidermidis. Compound 2 behaved synergistically with vancomycin against MRSA and was able to resensitize VRSA to vancomycin, reducing its MIC by 512-fold in two strains. In addition, both thiazole compounds were superior to vancomycin in significantly reducing S. epidermidis biofilm mass. Collectively, the results obtained demonstrate that compounds 1 and 2 possess potent antimicrobial activity alone or in combination with vancomycin against multidrug-resistant staphylococci and show potential for use in disrupting staphylococcal biofilm.