Ahuja Nidhi, Kumar Praveen, Bhatnagar Rakesh
Centre For Biotechnology, Jawaharlal Nehru University, New Delhi, India.
Crit Rev Microbiol. 2004;30(3):187-96. doi: 10.1080/10408410490468795.
Cyclic AMP is a ubiquitous messenger that integrates many processes of the cell. Diverse families of adenylate cyclases and phosphodiesterases stringently regulate the intracellular concentration of cAMP. Any alteration in the cytosolic concentration of cAMP has a profound effect on the various processes of the cell. Disruption of these cellular processes in vivo is often the most critical event in the pathogenesis of infectious diseases for animals and humans. Many pathogenic bacteria secrete toxins to alter the intracellular concentration of cAMP. These toxins either disrupt the normal regulation of the host cell's adenylate cyclases/phosphodiesterases or they themselves catalyze the synthesis of cAMP in the host cell. The latter are known as the adenylate cyclase toxins. Four such toxins have been identified: the invasive adenylate cyclase of Bordetella pertussis, the edema factor of Bacillus anthracis, ExoY of Pseudomonas aeruginosa, and the adenylate cyclase of Yersinia pestis. These adenylate cyclase toxins enter the eukaryotic host cells and get activated by eukaryotic cofactors, like calmodulin, to trigger the synthesis of cAMP in these cells. By accumulating cAMP in the target cells, these toxins either modulate the cellular function or completely deactivate the cell for further function. The immune effector cells appear to be the primary target of these adenylate cyclase toxins. By accumulating cAMP in the immune effector cells, these adenylate cyclase toxins poison the immune system and thus facilitate the survival of the bacteria in the host.
环磷酸腺苷(cAMP)是一种普遍存在的信使分子,它整合了细胞的许多过程。不同家族的腺苷酸环化酶和磷酸二酯酶严格调控细胞内cAMP的浓度。cAMP胞质浓度的任何改变都会对细胞的各种过程产生深远影响。在体内这些细胞过程的破坏通常是动物和人类传染病发病机制中最关键的事件。许多病原菌分泌毒素来改变细胞内cAMP的浓度。这些毒素要么破坏宿主细胞腺苷酸环化酶/磷酸二酯酶的正常调节,要么它们自身催化宿主细胞中cAMP的合成。后者被称为腺苷酸环化酶毒素。已鉴定出四种这样的毒素:百日咳博德特氏菌的侵袭性腺苷酸环化酶、炭疽芽孢杆菌的水肿因子、铜绿假单胞菌的ExoY以及鼠疫耶尔森菌的腺苷酸环化酶。这些腺苷酸环化酶毒素进入真核宿主细胞并被真核辅因子(如钙调蛋白)激活,从而触发这些细胞中cAMP的合成。通过在靶细胞中积累cAMP,这些毒素要么调节细胞功能,要么使细胞完全失活以停止进一步的功能。免疫效应细胞似乎是这些腺苷酸环化酶毒素的主要靶标。通过在免疫效应细胞中积累cAMP,这些腺苷酸环化酶毒素毒害免疫系统,从而促进细菌在宿主体内的存活。