Database screening and in vivo efficacy of antimicrobial peptides against methicillin-resistant Staphylococcus aureus USA300.

Database screening and in vivo efficacy of antimicrobial peptides against methicillin-resistant Staphylococcus aureus USA300.
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DOI:
10.1016/j.ijantimicag.2012.02.003
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发表时间:
2012-05
影响因子:
10.8
通讯作者:
Wang G
Wang G
中科院分区:
医学2区
文献类型:
--
作者:
Menousek J;Mishra B;Hanke ML;Heim CE;Kielian T;Wang G

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天然抗菌肽(AMPs)是开发新一代抗菌药物的候选药物,以应对耐甲氧西林金黄色葡萄球菌(MRSA)等抗生素耐药病原体的挑战。为了方便寻找新的候选者,我们利用了抗菌肽数据库(APD),其中包含来自细菌、真菌、植物和动物的天然AMP。这项研究通过筛选30个从apd中挑选的多肽,证明了针对MRSA的新模板的鉴定。这些多肽是短的(<25个残基),不含半胱氨酸,是阳离子的,代表了来自不同生物来源的候选物种,如细菌、昆虫、蜘蛛类、被毛类、两栖动物、鱼类和哺乳动物。对一株MRSA USA300分离株具有较强的抗菌活性,包括天花粉蛋白-8、数据库筛选的抗菌肽1(DASamP1)、DASamP2、狼毒毒素I、斑蛋白1.3和鱼腥草素1。虽然6个多肽中有5个具有广谱抗菌活性,但DASamP1在体外对MRSA有杀伤作用,而对大肠杆菌、枯草芽孢杆菌和铜绿假单胞菌没有杀伤作用。此外,在导管相关MRSA感染的小鼠模型中,DASamP1抑制了早期生物膜的形成。DASamP1是一种新颖、短小和有效的多肽,将为进一步开发新型抗MRSA多肽提供一个有用的起始模板。
Natural antimicrobial peptides (AMPs) are promising candidates for developing a generation of new antimicrobials to meet the challenge of antibiotic-resistant pathogens such as meticillin-resistant Staphylococcus aureus (MRSA). To facilitate the search for new candidates, we have utilised the Antimicrobial Peptide Database (APD), which contains natural AMPs from bacteria, fungi, plants and animals. This study demonstrates the identification of novel templates against MRSA by screening 30 peptides selected from the APD. These peptides are short (<25 residues), cysteine-free, cationic and represent candidates from different biological sources such as bacteria, insects, arachnids, tunicates, amphibians, fish and mammals. Six peptides, including ascaphin-8, database-screened antimicrobial peptide 1 (DASamP1), DASamP2, lycotoxin I, maculatin 1.3 and piscidin 1, were found to exert potent antimicrobial activity against an MRSA USA300 isolate. Although five of the six peptides showed broad-spectrum antibacterial activity, DASamP1 displayed killing of MRSA in vitro but not of Escherichia coli, Bacillus subtilis or Pseudomonas aeruginosa. In addition, DASamP1 suppressed early biofilm formation in a mouse model of catheter-associated MRSA infection. DASamP1 is a novel, short and potent peptide that will be a useful starting template for further developing novel anti-MRSA peptides.
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