Mycobacterial PE/PPE proteins at the host-pathogen interface

Abstract

The mycobacterial PE/PPE proteins have attracted much interest since their formal identification just over a decade ago. It has been widely speculated that these proteins may play a role in evasion of host immune responses, possibly via antigenic variation. Although a cohesive understanding of their function(s) has yet to be established, emerging data increasingly supports a role for the PE/PPE proteins at multiple levels of the infectious process. This paper will delineate salient features of the families revealed by comparative genomics, bioinformatic analyses and genome-wide screening approaches and will summarise existing knowledge of subcellular localization, secretion pathways, and protein structure. These characteristics will be considered in light of findings on innate and adaptive host responses to PE/PPE proteins, and we will review the increasing body of data on B and T cell recognition of these proteins. Finally, we will consider how current knowledge and future explorations may contribute to a more comprehensive understanding of these intriguing proteins and their involvement in host pathogen interactions. Ultimately this information could underpin future intervention strategies, for example, in the area of new and improved diagnostic tools and vaccine candidates.

Figure 1

Schematic representation of PE and PPE family subgroups. PE and PPE proteins possess relatively conserved N-terminal domains of approximately 110 aa and 180 aa, respectively. One subgroup of the PPE family incorporates a characteristic “SVP” motif at approximately 350 aa. Both PE and PPE families can be divided into distinct subgroups on the basis of their variable C-terminal domains. The regions encoded by the Polymorphic GC-Rich Sequence (PGRS) of the pe family and the Major Polymorphic Tandem Repeats (MPTR) of the ppe family are major contributors to genome polymorphism.