Abdallah Abdallah M, Verboom Theo, Weerdenburg Eveline M, Gey van Pittius Nicolaas C, Mahasha Phetole W, Jiménez Connie, Parra Marcela, Cadieux Nathalie, Brennan Michael J, Appelmelk Ben J, Bitter Wilbert
Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, the Netherlands.
Mol Microbiol. 2009 Aug;73(3):329-40. doi: 10.1111/j.1365-2958.2009.06783.x. Epub 2009 Jul 7.
ESX-5 is one of the five type VII secretion systems found in mycobacteria. These secretion systems are also known as ESAT-6-like secretion systems. Here, we have determined the secretome of ESX-5 by a proteomic approach in two different strains of Mycobacterium marinum. Comparison of the secretion profile of wild-type strains and their ESX-5 mutants showed that a number of PE_PGRS and PPE-MPTR proteins are dependent on ESX-5 for transport. The PE and PPE protein families are unique to mycobacteria, are highly expanded in several pathogenic species, such as Mycobacterium tuberculosis and M. marinum, and certain family members are cell surface antigens associated with virulence. Using a monoclonal antibody directed against the PGRS domain we showed that nearly all PE_PGRS proteins that are recognized by this antibody are missing in the supernatant of ESX-5 mutants. In addition to PE_PGRS and PPE proteins, the ESX-5 secretion system is responsible for the secretion of a ESAT-6-like proteins. Together, these data show that ESX-5 is probably a major secretion pathway for mycobacteria and that this system is responsible for the secretion of recently evolved PE_PGRS and PPE proteins.
ESX-5是分枝杆菌中发现的五种VII型分泌系统之一。这些分泌系统也被称为ESAT-6样分泌系统。在这里，我们通过蛋白质组学方法在两种不同的海分枝杆菌菌株中确定了ESX-5的分泌蛋白组。野生型菌株及其ESX-5突变体的分泌谱比较表明，许多PE_PGRS和PPE-MPTR蛋白的转运依赖于ESX-5。PE和PPE蛋白家族是分枝杆菌特有的，在几种致病物种中高度扩增，如结核分枝杆菌和海分枝杆菌，并且某些家族成员是与毒力相关的细胞表面抗原。使用针对PGRS结构域的单克隆抗体，我们发现该抗体识别的几乎所有PE_PGRS蛋白在ESX-5突变体的上清液中都缺失。除了PE_PGRS和PPE蛋白外，ESX-5分泌系统还负责一种ESAT-6样蛋白的分泌。总之，这些数据表明ESX-5可能是分枝杆菌的主要分泌途径，并且该系统负责最近进化的PE_PGRS和PPE蛋白的分泌。
