Mechanisms of adrenomedullin antimicrobial action

被引:62
作者
Allaker, RP
Grosvenor, PW
McAnerney, DC
Sheehan, BE
Srikanta, BH
Pell, K
Kapas, S
机构
[1] Univ London Queen Mary Coll, Inst Cell & Mol Sci, Imaging Unit, London E1 2AT, England
[2] Univ London Queen Mary Coll, Inst Cell & Mol Sci, Ctr Infect Dis, Bioinformat Grp, London E1 2AT, England
关键词
adrenomedullin; antimicrobial peptide; structure-function;
D O I
10.1016/j.peptides.2005.09.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mechanism of antimicrobial action of the multifunctional peptide adrenomedullin (AM) against Escherichia coli and Staphylococcus aureus was investigated. AM (52 residues) and AM fragments (1-12, 1-21, 13-2, 16-21, 16-52, 22-52, 26-52 and 34-52 residues) were tested for activity. Carboxy-terminal fragments were shown to be up to 250-fold more active than the parent molecule. Minimum inhibitory concentration values of the most active fragments (13-52 and 16-52) and the parent molecule were 4.9 x 10(-2) and 12.5 mu g/ml, respectively, with E. coli. Ultrastructural analyses of AM treated cells demonstrated marked cell wall disruption with E. coli within 0.5 h. Abnormal septum formation with no apparent peripheral cell wall disruption was observed with S. aureus after 2 h. Outer membrane permeabilisation assays with E. coli confirmed that the C-terminal fragments were significantly (P < 0.05) more active. It is suggested that postsecretory processing may generate multiple AM congeners that have enhanced antimicrobial activities against a range of potential targets. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:661 / 666
页数:6
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