Bacterial Effector-Involved Temporal and Spatial Regulation by Hijack of the Host Ubiquitin Pathway

Hiroki Nagai,Tomoko Kubori

doi:10.3389/fmicb.2011.00145

Abstract

Ubiquitination is one of the most conserved post-translational modifications of proteins, and is involved in essential eukaryotic cellular processes. These include protein degradation, transcriptional regulation, cell-cycle progression, and signaling. Microbial pathogens have evolved sophisticated systems to hijack host cellular functions for their own benefit. Central to these systems are protein transport machineries; many pathogenic bacteria inject “effector proteins” to modulate host cellular processes including the ubiquitin pathway. Numerous bacterial pathogens have been found to modulate the host ubiquitin system in various ways. In this review, we focus on three examples of temporal and spatial regulation of bacterial effectors, which are mediated by the host ubiquitin system. Subversion of the host ubiquitin system must be a widespread strategy among pathogenic bacteria to accomplish successful infection.

Highlights

Pathogenic bacteria have evolved specialized protein secretion systems to transfer a wide array of bacterial proteins into eukaryotic cells, exhibiting an intimate relationship between bacteria and host cells
It can be said that effector proteins play a key role in the hijacking of host cellular systems by bacteria
Virulence regulation by host ubiquitin subjected to proteasomal degradation with distinct half-lives; and (3) Salmonella effector SopB, the cellular localization of which is regulated by ubiquitination of the protein

Summary

INTRODUCTION

Pathogenic bacteria have evolved specialized protein secretion systems to transfer a wide array of bacterial proteins into eukaryotic cells, exhibiting an intimate relationship between bacteria and host cells. Referred to as type III, IV, and VI secretion systems, distinct types of “nanomachines” are used by pathogenic bacteria to directly inject bacterial proteins, so called “effector proteins,” into the host cell cytosol (Galan, 2001; Christie et al, 2005; Backert and Meyer, 2006; Galan and Wolf-Watz, 2006; Filloux et al, 2008) These effector proteins modulate many cellular processes essential for the establishment of infection, such as actin cytoskeleton rearrangement, vesicular trafficking manipulation, interference of numerous cellular signaling pathways, and escape of host immune systems (Galan, 2001; Waterman and Holden, 2003; Backert and Meyer, 2006; Pukatzki et al, 2009). We review three examples of ubiquitinmediated spatial or temporal regulation of bacterial effectors: (1) Legionella metaeffector LubX, which functions as an E3 ubiquitin ligase on another effector SidH, leading to proteasomal degradation; (2) Salmonella effectors SopE and SptP, both of which are www.frontiersin.org

Kubori and Nagai

CONCLUSION AND PERSPECTIVES