Periplasmic Targets for the Development of Effective Antimicrobials against Gram-Negative Bacteria

被引:26
作者
Pandeya, Ankit [1 ]
Ojo, Isoiza [1 ]
Alegun, Olaniyi [1 ]
Wei, Yinan [1 ]
机构
[1] Univ Kentucky, Dept Chem, Lexington, KY 40506 USA
来源
ACS INFECTIOUS DISEASES | 2020年 / 6卷 / 09期
关键词
antimicrobial resistance; periplasm; antimicrobial target; Gram-negative bacterium; inhibitor; efflux pump; chaperone; virulence; MULTIDRUG EFFLUX PUMP; DISULFIDE BOND FORMATION; OUTER-MEMBRANE PROTEIN; ESCHERICHIA-COLI; LIPOPOLYSACCHARIDE TRANSPORT; PSEUDOMONAS-AERUGINOSA; MOLECULAR CHAPERONE; CONFORMATIONAL-CHANGES; ANTIBIOTIC-RESISTANCE; CRYSTAL-STRUCTURE;
D O I
10.1021/acsinfecdis.0c00384
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Antibiotic resistance has emerged as a serious threat to global public health in recent years. Lack of novel antimicrobials, especially new classes of compounds, further aggravates the situation. For Gram-negative bacteria, their double layered cell envelope and an array of efflux pumps act as formidable barriers for antimicrobials to penetrate. While cytoplasmic targets are hard to reach, proteins in the periplasm are clearly more accessible, as the drug only needs to breach the outer membrane. In this review, we summarized recent efforts on the validation and testing of periplasmic proteins as potential antimicrobial targets and the development of related inhibitors that either inhibit the growth of a bacterial pathogen or reduce its virulence during interaction with host cells. We conclude that the periplasm contains a promising pool of novel antimicrobial targets that should be scrutinized more closely for the development of effective treatment against multidrug-resistant Gram-negative bacteria.
引用
收藏
页码:2337 / 2354
页数:18
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