Targeting BAM for Novel Therapeutics against Pathogenic Gram-Negative Bacteria.
Targeting BAM for Novel Therapeutics against Pathogenic Gram-Negative Bacteria.
复制标题
针对病原革兰氏阴性细菌的新型治疗剂的靶向BAM。
DOI：
10.3390/antibiotics12040679
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发表时间：
2023-03-30
影响因子：
4.8
通讯作者：
Noinaj, Nicholas
中科院分区：
文献类型：
--
作者：
Cottom, Claire Overly;Stephenson, Robert;Wilson, Lindsey;Noinaj, Nicholas
关键词：
细菌病原体中日益出现的多药耐药性是对全世界人类健康的直接威胁。不幸的是，新抗生素的发现并没有相应增加，以对抗这一令人担忧的趋势。针对革兰氏阴性细菌病原体的抗生素发现的新的当代方法已经将焦点扩大到还包括基本的表面暴露受体和蛋白质复合物，其经典地被靶向用于疫苗开发。最近引起关注的一种表面暴露的蛋白质复合物是β-桶组装机制（BAM），其在所有革兰氏阴性细菌中是保守的和必需的。BAM负责β-桶外膜蛋白（β-OMP）进入外膜的生物合成。这些β-OMPs对细胞起重要作用，包括营养摄取、信号传导和粘附，但也可以作为介导发病机制的毒力因子。已知BAM如何介导β-OMP生物发生的机制是动态和复杂的，提供了多种小分子抑制和较大生物制剂靶向的模式。在这篇综述中，我们介绍了BAM，并确定了为什么它是一个有前途的和令人兴奋的新的治疗靶点，并介绍了最近的研究报告新的化合物和疫苗靶向BAM在各种细菌。这些报告推动了对BAM正在进行和未来的研究，并提高了对BAM的兴趣，因为它在对抗革兰氏阴性细菌病原体的多药耐药性方面具有治疗前景。
The growing emergence of multidrug resistance in bacterial pathogens is an immediate threat to human health worldwide. Unfortunately, there has not been a matching increase in the discovery of new antibiotics to combat this alarming trend. Novel contemporary approaches aimed at antibiotic discovery against Gram-negative bacterial pathogens have expanded focus to also include essential surface-exposed receptors and protein complexes, which have classically been targeted for vaccine development. One surface-exposed protein complex that has gained recent attention is the β-barrel assembly machinery (BAM), which is conserved and essential across all Gram-negative bacteria. BAM is responsible for the biogenesis of β-barrel outer membrane proteins (β-OMPs) into the outer membrane. These β-OMPs serve essential roles for the cell including nutrient uptake, signaling, and adhesion, but can also serve as virulence factors mediating pathogenesis. The mechanism for how BAM mediates β-OMP biogenesis is known to be dynamic and complex, offering multiple modes for inhibition by small molecules and targeting by larger biologics. In this review, we introduce BAM and establish why it is a promising and exciting new therapeutic target and present recent studies reporting novel compounds and vaccines targeting BAM across various bacteria. These reports have fueled ongoing and future research on BAM and have boosted interest in BAM for its therapeutic promise in combatting multidrug resistance in Gram-negative bacterial pathogens.
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影响因子：
7.3
作者：
Grassmann AA;Kremer FS;Dos Santos JC;Souza JD;Pinto LDS;McBride AJA
通讯作者：
McBride AJA
影响因子：
3.7
作者：
Beard H;Cholleti A;Pearlman D;Sherman W;Loving KA
通讯作者：
Loving KA
影响因子：
3.7
作者：
Browning DF;Matthews SA;Rossiter AE;Sevastsyanovich YR;Jeeves M;Mason JL;Wells TJ;Wardius CA;Knowles TJ;Cunningham AF;Bavro VN;Overduin M;Henderson IR
通讯作者：
Henderson IR
DOI：
10.1126/science.aad3460
发表时间：
2016-01-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bakelar J;Buchanan SK;Noinaj N
通讯作者：
Noinaj N
BamA 蛋白作为小鼠大肠杆菌通用疫苗的计算机分析和重组表达
影响因子：
5
作者：
Guan, Qingfeng;Wang, Xiao;Wang, Jianhua
通讯作者：
Wang, Jianhua