Mohareer Krishnaveni, Tundup Smanla, Hasnain Seyed E
Institute of Life Sciences, Hyderabad, Indian Institute of Technology Delhi, New Delhi, India.
J Mol Microbiol Biotechnol. 2011;21(3-4):97-109. doi: 10.1159/000329489. Epub 2012 Jan 31.
The PE/PPE family of proteins, which constitute 10% of the coding capacity of the mycobacterial genome, comprises a unique set of genes which have no known homologs and have expanded throughout their evolution. Their association with virulence has been implicated by several researchers in tuberculosis, but the molecular basis of their virulence is yet to be completely explored. PE/PPE genes are mostly associated with the pathogenic strains of mycobacteria as many of them are known to be deleted in non-pathogenic ones. The non-essentiality of these genes for their in vitro growth but essentiality during infection highlights their active role in the host-pathogen interaction and consequently virulence. Even within the different strains of pathogenic mycobacteria and clinical isolates, many of the PE/PPE genes show sequence variation, pointing to their importance in providing antigenic variations, and have also been speculated to perform varied roles by differential expression during host-pathogen interaction. The transcriptional regulators of these genes could therefore act as a molecular switch for the pathogenesis of Mycobacterium tuberculosis. This review focuses on the expression and regulation of PE/PPE genes in the context of infection and pathogenicity and discusses the potential of these proteins as drug targets.
PE/PPE蛋白家族占分枝杆菌基因组编码能力的10%，由一组独特的基因组成，这些基因没有已知的同源物，并且在其整个进化过程中不断扩增。几位研究人员认为它们与结核病的毒力有关，但其毒力的分子基础尚未完全阐明。PE/PPE基因大多与分枝杆菌的致病菌株相关，因为已知其中许多基因在非致病菌株中缺失。这些基因对其体外生长并非必需，但在感染过程中却是必需的，这突出了它们在宿主-病原体相互作用以及毒力方面的积极作用。即使在致病分枝杆菌的不同菌株和临床分离株中，许多PE/PPE基因也表现出序列变异，表明它们在提供抗原变异方面的重要性，并且据推测在宿主-病原体相互作用期间通过差异表达发挥多种作用。因此，这些基因的转录调节因子可能是结核分枝杆菌发病机制的分子开关。本综述重点关注PE/PPE基因在感染和致病性背景下的表达和调控，并讨论这些蛋白作为药物靶点的潜力。
