An inhibitor of gram-negative bacterial virulence protein secretion.
An inhibitor of gram-negative bacterial virulence protein secretion.
复制标题
革兰氏阴性细菌毒力蛋白分泌的抑制剂。
DOI：
10.1016/j.chom.2008.08.001
复制
发表时间：
2008-10-16
影响因子：
30.3
通讯作者：
Miller SI
中科院分区：
文献类型：
--
作者：
Felise HB;Nguyen HV;Pfuetzner RA;Barry KC;Jackson SR;Blanc MP;Bronstein PA;Kline T;Miller SI
细菌毒力机制是抗生素开发的有吸引力的目标，因为它们是许多全球传染病病原体致病所必需的。细菌分泌系统用来组装促进黏附和向宿主细胞运送蛋白毒力效应物的表面结构，可能包括一个这样的治疗靶点。在这项研究中，我们开发并进行了小分子文库的高通量筛选(HTS)，并鉴定了一个小分子，即2-亚氨基-5-芳基噻唑烷酮，它能阻断大量动植物革兰氏阴性细菌的分泌和毒力功能。该化合物抑制III型分泌依赖功能(鞭毛运动除外)和II型分泌依赖功能，提示该化合物的靶标可能是介于这两个分泌系统之间的外膜成分。这项工作提供了一个概念证明，具有广谱抗革兰氏阴性细菌分泌系统活性的化合物可以被开发出来预防和治疗细菌疾病。
Bacterial virulence mechanisms are attractive targets for antibiotic development, because they are required for the pathogenesis of numerous global infectious disease agents. The bacterial secretion systems used to assemble the surface structures that promote adherence and deliver protein virulence effectors to host cells could comprise one such therapeutic target. In this study, we developed and performed a high-throughput screen (HTS) of small molecule libraries and identified a small molecule, a 2-imino-5-arylidene thiazolidinone that blocked secretion and virulence functions of a wide array of animal and plant Gram-negative bacterial pathogens. This compound inhibited type III secretion-dependent functions, with the exception of flagellar motility, and Type II secretion-dependent functions, suggesting that the target of the compound could be an outer membrane component conserved between these two secretion systems. This work provides a proof of concept that compounds with a broad spectrum of activity against Gram-negative bacterial secretion systems could be developed to prevent and treat bacterial diseases.
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影响因子：
3.1
作者：
Nordfelth, R;Kauppi, AM;Elofsson, M
通讯作者：
Elofsson, M
影响因子：
3.2
作者：
Guilvout, I;Hardie, KR;Pugsley, AP
通讯作者：
Pugsley, AP
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
3.6
作者：
Matsumoto, H;Young, GM
通讯作者：
Young, GM
DOI：
10.1073/pnas.200209497
发表时间：
2000-09-26
影响因子：
11.1
作者：
Kimbrough, TG;Miller, SI
通讯作者：
Miller, SI