Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant Staphylococci

被引：80
作者：
Mohammad, Haroon [1 ]
Mayhoub, Abdelrahman S. [2 ]
Cushman, Mark [3 ,4 ]
Seleem, Mohamed N. [1 ]
机构：
[1] Purdue Univ, Dept Comparat Pathobiol, Coll Vet Med, W Lafayette, IN 47907 USA
[2] Al Azhar Univ, Dept Organ Chem, Cairo, Egypt
[3] Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA
[4] Purdue Ctr Canc Res, W Lafayette, IN USA
来源：
JOURNAL OF ANTIBIOTICS | 2015年 / 68卷 / 04期
关键词：
ANTIMICROBIAL COMBINATIONS; AUREUS INFECTIONS; DERIVATIVES; DISCOVERY; POTENT; VANCOMYCIN; MECHANISMS; INHIBITORS; PEPTIDES; AGENTS;
D O I：
10.1038/ja.2014.142
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
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.
引用
收藏
页码：259 / 266
页数：8
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