Shigella Infection Interferes with SUMOylation and Increases PML-NB Number

Abstract

Shigellosis is a severe diarrheal disease that affects hundreds of thousands of individuals resulting in significant morbidity and mortality worldwide. Shigellosis is caused by Shigella spp., a gram-negative bacterium that uses a Type 3 Secretion System (T3SS) to deliver effector proteins into the cytosol of infected human cells. Shigella infection triggers multiple signaling programs that result in a robust host transcriptional response that includes the induction of multiple proinflammatory cytokines. PML nuclear bodies (PML-NBs) are dynamic subnuclear structures that coordinate immune signaling programs and have a demonstrated role in controlling viral infection. We show that PML-NB number increases upon Shigella infection. We examined the effects of Shigella infection on SUMOylation and found that upon Shigella infection the localization of SUMOylated proteins is altered and the level of SUMOylated proteins decreases. Although Shigella infection does not alter the abundance of SUMO activating enzymes SAE1 or SAE2, it dramatically decreases the level of the SUMO conjugating enzyme Ubc9. All Shigella-induced alterations to the SUMOylation system are dependent upon a T3SS. Thus, we demonstrate that Shigella uses one or more T3SS effectors to influence both PML-NB number and the SUMOylation machinery in human cells.

Promyelocytic Leukemia Protein (PML) ControlsListeria monocytogenesInfection

“…Further characterization of the putative PML-regulated genes induced during Salmonella infection or the effect of Salmonella on PML SUMOylation/multimerization will be required to fully understand the differences in PML-dependent sensitivity between Listeria and Salmonella . Interestingly, Shigella flexneri , in addition to its effect on the Ubc9 level, was shown to induce a two-fold increase in the number of PML NBs in HeLa cells, which was not observed during incubation with a non-invasive avirulent strain (22). The putative role of PML in Shigella infection, however, remains unknown.…”

“…Infection of HeLa cells with Shigella flexneri , a pathogen causing bacillary dysentery, leads to a decrease in Ubc9 level and a modification of host SUMOylated proteins (22, 23). Transcription factors involved in inflammatory responses, such as c-FOS, RXRα, and PPAR γ, for example, are de-SUMOylated in response to Shigella infection (23).…”

Klebsiella pneumoniaereduces SUMOylation to limit host defence responses

“…To date, it has been shown that the intracellular pathogens Listeria monocytogenes, Shigella and Salmonella typhimurium trigger an overall decrease in SUMOylation of proteins [5][6][7]. The three pathogens induce the degradation of the E2 enzyme Ubc9 to decrease the amount of SUMO conjugates [5][6][7], indicating that depletion of Ubc9 could be a preferred bacterial strategy to target SUMOylation. Recently, S. flexneri has also been shown to trigger the degradation of the SUMO E1 enzyme SAE2 to reduce SUMOylation [8].…”

Estudos da dinâmica do núcleo da célula hospedeira durante a infecção por Trypanosoma cruzi

“…Muitas pesquisas estão focadas em encontrar novas evidencias científicas sobre as incógnitas que ainda restam com relação à interação entre diversos tipos de patógenos com a célula hospedeira (Finlay et al, 1997;Nathan et al, 2000;Lamaire et al, 2013;Strang, 2014;Isnard et al, 2015;Sidik et al, 2015). Bergonioux et al, 2012;Sidik et al, 2015). Já a SUMOilação, que é um processo de modificação pós-traducional, interfere na infecção bacteriana (Dunphy et al, 2014).…”

“…Já a SUMOilação, que é um processo de modificação pós-traducional, interfere na infecção bacteriana (Dunphy et al, 2014). O patógeno pode empregar esse processo para regular o destino de seus determinantes de virulência, a fim de facilitar sua sobrevivência dentro da célula do hospedeiro (Fritah et al, 2014;Sidik et al, 2015).…”