Mycobacterial PE/PPE Proteins at the Host-Pathogen Interface

Samantha L Sampson

doi:10.1155/2011/497203

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.

Highlights

Tuberculosis (TB) represents an ongoing threat to global health, with the current epidemic fuelled by HIV-coinfection and an increasing incidence of drug resistant strains of Mycobacterium tuberculosis [1]
The first M. tuberculosis genome sequence was completed, and it was revealed that these variable regions were part of two extensive families encoding almost 200 putative proteins [5]
Gao et al examined gene expression in 10 clinical isolates of M. tuberculosis and found that 28 of the 77 pe/ppe genes included in the analysis showed variable expression [29]

Summary

Introduction

Tuberculosis (TB) represents an ongoing threat to global health, with the current epidemic fuelled by HIV-coinfection and an increasing incidence of drug resistant strains of Mycobacterium tuberculosis [1]. B cells are likely to be more important in determining the outcome of infection with M. tuberculosis than previously supposed, and ignoring this aspect of the host immune response may restrict our understanding of TB immunopathology In this context, PE/PPE family members are a potentially rich source of B cell epitopes, and a number of PE/PPE proteins may be surface exposed, increasing the likelihood that they could be targeted by the humoral response. A recent study which combined multiple genome sequence comparisons with analysis of published immunogenicity data reported an unexpectedly high level of conservation of human T cell epitopes [86] This runs counter to the existing dogma that antigenic targets will exhibit a relatively high degree of variation due to selection pressures imposed by host immune responses. There is substantial evidence that these proteins contribute to immune evasion via other important mechanisms, as described above

Translational Applications

Findings

Conclusions