Directed delivery of heat-labile enterotoxin by enterotoxigenic Escherichia coli
Directed delivery of heat-labile enterotoxin by enterotoxigenic Escherichia coli
复制标题
DOI：
10.1111/j.1462-5822.2006.00736.x
复制
发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Fleckenstein, James M.
中科院分区：
文献类型：
--
作者：
Dorsey, F. Chuck;Fischer, Julia F.;Fleckenstein, James M.
产肠毒素大肠杆菌（ETEC）是发展中国家腹泻发病率和死亡率的主要原因，它是一种异质性病原体，产生热不稳定（LT）和/或热稳定（ST）肠毒素，引起水样霍乱样腹泻。允许LT有效递送的分子事件仍不确定。在这里，我们描述了宿主-病原体相互作用的作用，因为它与ETEC的LT递送有关。通过半透性过滤器将细菌与靶肠上皮单层分离，防止腺苷酸环化酶的活化，这表明病原体-宿主细胞接触是有效递送毒素所必需的。同样地，相对于ETEC（H10407）原型，鞭毛fliD基因突变的非运动型菌株在LT递送方面存在缺陷。虽然LT分泌通过II型分泌系统（T2 SS）是响应于各种环境因素，无论是毒素的释放，也不交付依赖于转录激活的基因编码LT或T2 SS。绿色荧光蛋白与GspM（LT的T2 SS系统的组分）和LT的融合表明T2 SS和毒素都分布在ETEC细菌的一个极点。最佳LT递送可以以极化方式发生，在与宿主细胞密切相互作用后转移预先形成的毒素，防止LT中和。
Enterotoxigenic Escherichia coli (ETEC), leading causes of diarrhoeal morbidity and mortality in developing countries, are heterogenous pathogens that elaborate heat-labile (LT) and/or heat-stable (ST) enterotoxins which elicit watery, cholera-like diarrhoea. The molecular events permitting efficient delivery of LT remain undefined. Here, we characterize the role of host-pathogen interaction as it relates to the delivery of LT by ETEC. Separation of bacteria from target intestinal epithelial monolayers by semipermeable filters prevented activation of adenylate cyclase suggesting that pathogen-host cell contact is required for efficient toxin delivery. Likewise, a non-motile strain bearing a mutation in the flagellar fliD gene was deficient in delivery of LT relative to the ETEC (H10407) prototype. Although LT secretion via the type II secretion system (T2SS) was responsive to a variety of environmental factors, neither toxin release nor delivery depended on transcriptional activation of genes encoding LT or the T2SS. Fusions of green fluorescent protein to GspM (a component of the T2SS system for LT) and to LT demonstrated that both T2SS and toxin are distributed at one pole of the ETEC bacterium. Optimal LT delivery may occur in a polarized fashion with transfer of preformed toxin upon close interaction with host cells, preventing neutralization of LT.