Transcriptional regulation of Mycobacterium tuberculosis PE/PPE genes: a molecular switch to virulence?

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.