Telomere components as potential therapeutic targets for treating microbial pathogen infections

Bibo Li

doi:10.3389/fonc.2012.00156

Abstract

In a number of microbial pathogens that undergoes antigenic variation to evade the host’s immune attack, genes encoding surface antigens are located at subtelomeric loci, and recent studies have revealed that telomere components play important roles in regulation of surface antigen expression in several of these pathogens, indicating that telomeres play critical roles in microbial pathogen virulence regulation. Importantly, although telomere protein components and their functions are largely conserved from protozoa to mammals, telomere protein homologs in microbial pathogens and humans have low sequence homology. Therefore, pathogen telomere components are potential drug targets for therapeutic approaches because first, most telomere proteins are essential for pathogens’ survival, and second, disruption of pathogens’ antigenic variation mechanism would facilitate host’s immune system to clear the infection.

Highlights

Telomeres are nucleoprotein complexes located at the ends of linear chromosomes
The core telomere protein complex termed “Shelterin” contains two duplex TTAGGG repeat binding factors, TRF1 and TRF2 (Chong et al, 1995; Bilaud et al, 1997; Broccoli et al, 1997), a single-stranded telomere DNA binding protein, POT1 (Baumann and Cech, 2001), and RAP1 (Li et al, 2000), TIN2 (Kim et al, 1999), and TPP1 (Houghtaling et al, 2004; Liu et al, 2004; Ye et al, 2004) that interact with TRFs or POT1
Fission yeast has a very similar telomere protein complex (Miyoshi et al, 2008), and many telomere protein homologs have been identified in budding yeast, too (Lewis and Wuttke, 2012)

Summary

Bibo Li*

Reviewed by: Karel Riha, Gregor Mendel Institute, Austria Lin Liu, Nankai University, China. In a number of microbial pathogens that undergoes antigenic variation to evade the host’s immune attack, genes encoding surface antigens are located at subtelomeric loci, and recent studies have revealed that telomere components play important roles in regulation of surface antigen expression in several of these pathogens, indicating that telomeres play critical roles in microbial pathogen virulence regulation. Pathogen telomere components are potential drug targets for therapeutic approaches because first, most telomere proteins are essential for pathogens’ survival, and second, disruption of pathogens’ antigenic variation mechanism would facilitate host’s immune system to clear the infection

INTRODUCTION

Findings

Telomeres and microbial pathogen virulence