Broad-spectrum peptide inhibitors of aminoglycoside antibotic resistance enzymes

被引:69
作者
Boehr, DD
Draker, KA
Koteva, K
Bains, M
Hancock, RE
Wright, GD
机构
[1] McMaster Univ, Dept Biochem, Antimicrobial Res Ctr, Hamilton, ON L8N 3Z5, Canada
[2] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada
来源
CHEMISTRY & BIOLOGY | 2003年 / 10卷 / 02期
基金
加拿大健康研究院;
关键词
D O I
10.1016/S1074-5521(03)00026-7
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 action of aminoglycoside antibiotics is inhibited by chemical modification catalyzed by aminoglycoside inactivating enzymes, which bind these cationic saccharides with active site pockets that contain a preponderance of negatively charged residues. In this study, it was observed that several cationic antimicrobial peptides, representing different structural classes, could serve as inhibitors of such aminoglycoside resistance enzymes. The bovine antimicrobial peptide indolicidin and synthetic analogs appeared to be especially effective against a range of resistance enzymes, inhibiting enzymes belonging to both aminoglycoside phosphotransferase and aminoglycoside acetyltransferase classes, where the mode of action was dependent on the class of antibiotic resistance enzyme. These peptides represent the first example of broad-spectrum inhibitors of aminoglycoside resistance enzymes.
引用
收藏
页码:189 / 196
页数:8
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