Abdallah Abdallah M, Verboom Theo, Hannes Fredericke, Safi Mohamad, Strong Michael, Eisenberg David, Musters René J P, Vandenbroucke-Grauls Christina M J E, Appelmelk Ben J, Luirink Joen, Bitter Wilbert
Department of Medical Microbiology and Infection Control, VU Medical Centre, Amsterdam, the Netherlands.
Mol Microbiol. 2006 Nov;62(3):667-79. doi: 10.1111/j.1365-2958.2006.05409.x.
Mycobacterial genomes contain two unique gene families, the so-called PE and PPE gene families, which are highly expanded in the pathogenic members of this genus. Here we report that one of the PPE proteins, i.e. PPE41, is secreted by pathogenic mycobacteria, both in culture and in infected macrophages. As PPE41 lacks a signal sequence a dedicated secretion system must be involved. A single gene was identified in Mycobacterium marinum that showed strongly reduced PPE41 secretion. This gene was located in a gene cluster whose predicted proteins encode components of an ESAT-6-like secretion system. This cluster, designated ESX-5, is conserved in various pathogenic mycobacteria, but not in the saprophytic species Mycobacterium smegmatis. Therefore, different regions of this cluster were introduced in M. smegmatis. Only introduction of the complete ESX-5 locus resulted in efficient secretion of heterologously expressed PPE41. This PPE secretion system is also involved in the virulence of pathogenic mycobacteria, as the ESX-5 mutant of M. marinum was affected in spreading to uninfected macrophages.
分枝杆菌基因组包含两个独特的基因家族，即所谓的PE和PPE基因家族，它们在该属的致病成员中高度扩增。在此我们报告，一种PPE蛋白，即PPE41，在培养物中和感染的巨噬细胞中均由致病性分枝杆菌分泌。由于PPE41缺乏信号序列，必然涉及一种专门的分泌系统。在海分枝杆菌中鉴定出一个单一基因，该基因显示PPE41分泌大幅减少。该基因位于一个基因簇中，其预测的蛋白质编码一种ESAT-6样分泌系统的组分。这个被命名为ESX-5的基因簇在各种致病性分枝杆菌中保守，但在腐生菌耻垢分枝杆菌中不存在。因此，将该基因簇的不同区域导入耻垢分枝杆菌。只有导入完整的ESX-5基因座才能有效分泌异源表达的PPE41。这种PPE分泌系统也参与致病性分枝杆菌的毒力，因为海分枝杆菌的ESX-5突变体在向未感染的巨噬细胞扩散方面受到影响。
