Gelatinase biosynthesis-activating pheromone:: a peptide lactone that mediates a quorum sensing in Enterococcus faecalis

Gelatinase biosynthesis-activating pheromone:: a peptide lactone that mediates a quorum sensing in Enterococcus faecalis
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DOI:
10.1046/j.1365-2958.2001.02486.x
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发表时间:
2001-07-01
影响因子:
3.6
通讯作者:
Nagasawa, H
Nagasawa, H
中科院分区:
生物学2区
文献类型:
--
作者:
Nakayama, J;Cao, Y;Nagasawa, H

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明胶酶是粪肠球菌的一种毒力因子,其生物合成被发现以细胞密度依赖的方式调节,其生产在后期到早期稳定期活跃。在培养基中加入早期固定化培养滤液将明胶酶生产的开始时间转移到中期,这表明粪肠杆菌分泌一种明胶酶生物合成激活信息素(GBAP)。从粪肠杆菌OG1S-P培养上清液中分离到gbp。结构分析表明,gbp是含有内酯结构的11个残基环肽,其中c端氨基酸的α -羧基与第三个残基丝氨酸的羟基相连。一个具有推导出的结构的合成肽在纳摩尔浓度下表现出与天然gbp一样的gbp活性。数据库检索显示,gap对应于242个残基的FsrB蛋白的c端部分。Northern分析显示,ggbap缓慢诱导两个操纵子的转录,分别是编码FsrB的FsrB - FsrC和编码明胶酶GelE和丝氨酸蛋白酶SprE的组氨酸激酶FsrC和GelE - SprE。在fsrC或应答调节基因fsrA中插入突变的菌株对GBAP没有应答,这表明GBAP信号是由双组分调控系统转导的。
Biosynthesis of gelatinase, a virulence factor of Enterococcus faecalis, was found to be regulated in a cell density-dependent fashion in which its production is active in late log to early stationary phase. Addition of early stationary phase culture filtrate to medium shifted the onset of gelatinase production to that of mid-log phase, suggesting that E. faecalis secretes a gelatinase biosynthesis-activating pheromone (GBAP). GBAP was isolated from culture supernatant of E. faecalis OG1S-P. Structural analysis suggested GBAP to be an 11-residue cyclic peptide containing a lactone structure, in which the alpha -carboxyl group of the C-terminal amino acid is linked to a hydroxyl group of the serine of the third residue. A synthetic peptide possessing the deduced structure showed GBAP activity at nanomolar concentrations as did natural GBAP. Database searches revealed that GBAP corresponds to a C-terminal part of a 242-residue FsrB protein. Northern analysis showed that GBAP slowly induces the transcription of two operons, fsrB-fsrC encoding FsrB and a putative histidine kinase FsrC and gelE-sprE encoding gelatinase GelE and serine protease SprE. Strains with an insertion mutation in either fsrC or a putative response regulator gene fsrA failed to respond to GBAP, suggesting that the GBAP signal is transduced by a two-component regulatory system.