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A short artificial antimicrobial peptide shows potential to prevent or treat bone infections

机译:短的人工抗菌肽显示出预防或治疗骨感染的潜力

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摘要

Infection of bone is a severe complication due to the variety of bacteria causing it, their resistance against classical antibiotics, the formation of a biofilm and the difficulty to eradicate it. Antimicrobial peptides (AMPs) are naturally occurring peptides and promising candidates for treatment of joint infections. This study aimed to analyze the effect of short artificial peptides derived from an optimized library regarding (1) antimicrobial effect on different bacterial species, (2) efficacy on biofilms, and (3) effect on osteoblast‑like cells. Culturing the AMP-modifications with Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus (including clinical isolates of MRSA and MSSA) and Staphylococcus epidermidis identified one candidate that was most effective against all bacteria. This AMP was also able to reduce biofilm as demonstrated by FISH and microcalorimetry. Osteoblast viability and differentiation were not negatively affected by the AMP. A cation concentration comparable to that physiologically occurring in blood had almost no negative effect on AMP activity and even with 10% serum bacterial growth was inhibited. Bacteria internalized into osteoblasts were reduced by the AMP. Taken together the results demonstrate a high antimicrobial activity of the AMP even against bacteria incorporated in a biofilm or internalized into cells without harming human osteoblasts.
机译:由于引起骨骼的细菌种类繁多,对经典抗生素的抵抗力,生物膜的形成以及根除细菌的困难,骨骼感染是一种严重的并发症。抗菌肽(AMPs)是天然存在的肽,有望用于治疗关节感染。这项研究旨在分析源自优化文库的短人工肽在以下方面的作用:(1)对不同细菌种类的抗菌作用,(2)对生物膜的功效以及(3)对成骨细胞样细胞的作用。用大肠杆菌,粪肠球菌,铜绿假单胞菌,金黄色葡萄球菌(包括MRSA和MSSA的临床分离株)和表皮葡萄球菌培养AMP修饰物,可以确定一种对所有细菌最有效的候选物。如FISH和微量量热法所证明,该AMP还能够减少生物膜。成骨细胞的活力和分化不受AMP的负面影响。阳离子浓度与血液中的生理浓度相当,对AMP活性几乎没有负面影响,甚至血清细菌的生长也被抑制10%。 AMP减少了内在成骨细胞的细菌。综上所述,结果表明,AMP甚至对掺入生物膜或内化到细胞内的细菌均具有很高的抗菌活性,而不会损害人类成骨细胞。

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