Trojan horse strategies used by pathogens to influence the small ubiquitin-like modifier (SUMO) system of host eukaryotic cells

Abstract

A remarkable feature of pathogenic organisms is their ability to utilize the cellular machinery of host cells to their advantage in facilitating their survival and propagation. Posttranslational modification of proteins offers a quick way to achieve changes in the localization, binding partners or functions of a target protein. It is no surprise then that pathogens have evolved multiple ways to interfere with host posttranslational modifications and hijack them for their own purposes. Recently, modification of proteins by small ubiquitin-like modifier has emerged as an important posttranslational modification regulating transcription, DNA repair and cell division, and literature has started to emerge documenting how it could be utilized by pathogenic bacteria and viruses during infection. In this brief review, we focus on the host small ubiquitin-like modifier (SUMO) system and how disease causing agents influence SUMO conjugation and deconjugation, highlighting the common theme of global hypoSUMOylation upon infection by pathogens.

Fig. 1

SUMOylation/deSUMOylation dynamics: the SUMO pathway in eukaryotes, depicting SUMO activation by E1, SUMO ligation by the E2 and E3 enzymes onto target proteins, and subsequent SUMO deconjugation by SUMO proteases, which also process SUMO to its active form.

Fig. 2

The functions of XopD in bacterial infection of plant cells: the injection of XopD into host plant cells by the TTSS of X. campestris pathovar vesicatoria. Upon delivery, XopD translocates to the nucleus and deSUMOylates nuclear SUMOylated proteins, presumably turning off the transcription of genes required for plant defense mechanisms. It is currently unclear if XopD performs additional deSUMOylating activities in the plant cytosol or whether XopD can cleave SUMO chains.

Fig. 3

The influence of pathogens on the host SUMOylation pathway: examples of a viral protein [Gam1 from adenovirus CELO (in blue)] and a bacterial virulence factor [lysteriolysin O from L. monocytogenes (in pink)] influencing the SUMO pathway of host cells upon infection, resulting in global hypoSUMOylation of target proteins.