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脑膜炎奈瑟菌与人上皮细胞的紧密黏附受crgA基因控制,该基因是一种新型的LysR型转录调节因子。

Intimate adhesion of Neisseria meningitidis to human epithelial cells is under the control of the crgA gene, a novel LysR-type transcriptional regulator.

作者信息

Deghmane A E, Petit S, Topilko A, Pereira Y, Giorgini D, Larribe M, Taha M K

机构信息

Unité des Neisseria, Institut Pasteur, 25, 28 Rue du Dr Roux, 75724 Paris, Cedex 15, France.

出版信息

EMBO J. 2000 Mar 1;19(5):1068-78. doi: 10.1093/emboj/19.5.1068.

Abstract

PilC1, a pilus-associated protein in Neisseria menin- gitidis, is a key element in initial meningococcal adhesion to target cells. A promoter element (CREN, contact regulatory element of Neisseria) is responsible for the transient induction of this gene upon cell contact. crgA (contact-regulated gene A) encodes a transcriptional regulator whose expression is also induced upon cell contact from a promoter region similar to the CREN of pilC1. CrgA shows significant sequence homologies to LysR-type transcriptional regulators. Its inactivation in meningococci provokes a dramatic reduction in bacterial adhesion to epithelial cells. Moreover, this mutant is unable to undergo intimate adhesion to epithelial cells or to provoke effacing of microvilli on infected cells. Purified CrgA is able to bind to pilC1 and crgA promoters, and CrgA seems to repress the expression of pilC1 and crgA. Our results support a dynamic model of bacteria-cell interaction involving a network of regulators acting in cascade. CrgA could be an intermediate regulator in such a network.

摘要

PilC1是脑膜炎奈瑟菌中一种与菌毛相关的蛋白质,是脑膜炎奈瑟菌最初黏附于靶细胞的关键因素。一种启动子元件(CREN,奈瑟菌接触调节元件)负责在细胞接触时短暂诱导该基因表达。crgA(接触调节基因A)编码一种转录调节因子,其表达在细胞接触时也从与pilC1的CREN相似的启动子区域被诱导。CrgA与LysR型转录调节因子具有显著的序列同源性。其在脑膜炎奈瑟菌中的失活导致细菌对上皮细胞的黏附显著减少。此外,该突变体无法与上皮细胞进行紧密黏附,也无法引起感染细胞微绒毛的消失。纯化的CrgA能够结合pilC1和crgA启动子,并且CrgA似乎抑制pilC1和crgA的表达。我们的结果支持一种涉及级联作用的调节因子网络的细菌 - 细胞相互作用动态模型。CrgA可能是这样一个网络中的中间调节因子。

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