Department of Microbiology and Pathology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, USA.
Int J Antimicrob Agents. 2012 May;39(5):402-6. doi: 10.1016/j.ijantimicag.2012.02.003. Epub 2012 Mar 23.
Natural antimicrobial peptides (AMPs) are promising candidates for developing a generation of new antimicrobials to meet the challenge of antibiotic-resistant pathogens such as methicillin-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.
天然抗菌肽 (AMPs) 是开发新一代抗菌药物的有前途的候选物，可用于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物，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。本研究通过筛选 APD 中的 30 种肽来证明针对 MRSA 的新型模板的鉴定。这些肽是短的 (<25 个残基)、不含半胱氨酸、阳离子，代表来自不同生物来源的候选物，如细菌、昆虫、蛛形纲动物、被囊动物、两栖动物、鱼类和哺乳动物。六种肽，包括 ascaphin-8、数据库筛选的抗菌肽 1 (DASamP1)、DASamP2、lycotoxin I、maculatin 1.3 和 piscidin 1，被发现对 MRSA USA300 分离株具有强大的抗菌活性。尽管这六种肽中的五种显示出广谱的抗菌活性，但 DASamP1 在体外显示出对 MRSA 的杀伤作用，但对大肠杆菌、枯草芽孢杆菌或铜绿假单胞菌没有作用。此外，DASamP1 抑制了 MRSA 导管相关性感染小鼠模型中的早期生物膜形成。DASamP1 是一种新型的、短的、有效的肽，将成为进一步开发新型抗 MRSA 肽的有用起始模板。
