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

被引:28
作者
Bormann, N. [1 ,2 ]
Koliszak, A. [1 ,3 ]
Kasper, S. [1 ]
Schoen, L. [1 ]
Hilpert, K. [4 ]
Volkmer, R. [5 ,8 ]
Kikhney, J. [6 ,7 ]
Wildemann, B. [1 ,2 ,3 ]
机构
[1] Charite, Julius Wolff Inst, Berlin, Germany
[2] Charite, Berlin Brandenburg Ctr Regenerat Therapies, Berlin, Germany
[3] Charite, Ctr Musculoskeletal Surg, Berlin, Germany
[4] St Georges Univ London, Inst Infect & Immun, London, England
[5] Charite, Inst Med Immunol, Berlin, Germany
[6] Charite, Inst Microbiol & Hyg, Berlin, Germany
[7] German Heart Inst Berlin, Biofilmctr, Berlin, Germany
[8] Leibniz Inst Mol Pharmacol, Berlin, Germany
关键词
IN-SITU HYBRIDIZATION; GRAM-NEGATIVE BACTERIA; STAPHYLOCOCCUS-EPIDERMIDIS; IDENTIFICATION; ANTIBIOTICS; GENTAMICIN; VITRO; DESIGN; POLYSACCHARIDE; BIOMATERIALS;
D O I
10.1038/s41598-017-01698-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
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.
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页数:14
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