Strain Variation in the Mycobacterium tuberculosis Complex: Its Role in Biology, Epidemiology and Control

Giovanni Delogu, Michael J. Brennan, Riccardo Manganelli

PE and PPE are two large families of proteins typical of mycobacteria whose structural genes in the Mycobacterium tuberculosis complex (MTBC) occupy about 7% of the total genome. The most ancestral PE and PPE proteins are expressed by genes that belong to the same operon and in most cases are found inserted in the esx clusters, encoding a type VII secretion system. Duplication and expansion of pe and ppe genes, coupled with intragenomic and intergenomic recombination events, led to the emergence of the polymorphic pe_pgrs and ppe_mptr genes in the MTBC genome. The role and function of these proteins, and particularly of the polymorphic subfamilies, remains elusive, although it is widely accepted that PE and PPE proteins may represent a specialized collection used by MTBC to interact with the complex host immune system of mammals. In this chapter, we summarize what has been discovered since the identification of these genes in 1998, focusing on M. tuberculosis genetic variability, host-pathogen interaction and TB pathogenesis.