Mechanism of type VI secretion system 5-dependent intercellular spread of Burkholderia pseudomallei
Final Report Abstract
The human pathogen Burkholderia pseudomallei and the related species Burkholderia thailandensis are facultative intracellular bacteria that employ the type VI secretion system (T6SS-5) to spread to an uninfected host cell in a direct manner. The dissemination is mediated by the fusion of the plasma membrane of the infected and uninfected neighboring cell which leads to the formation of multinucleated giant cells and requires T6SS-5 activity. Given the essential role of the T6SS-5 in virulence surprisingly little is known about the mechanism underlying the fusion process and the host cell factors involved. We focused our analysis on the only T6SS-5-secreted protein with putative effector activity, VgrG-5, and identified regions of the protein that influence the localization of the protein inside host cells. Furthermore, we investigated the role of host cell surface proteins and cholesterol in T6SS-6-induced cell-cell fusion as these factors are important for giant cell formation stimulated by viruses. Using acute proteolytic treatment or acute cholesterol depletion of macrophages infected with B. thailandensis we found that proteins exposed on the host cell surface as well as cholesterol are involved in T6SS-5-stimulated membrane fusion. Altogether, the data indicate that the T6SS-5 does not act independently of host cell factors.
Publications
- (2017) Cholesterol and host cell surface proteins contribute to cell-cell fusion induced by the Burkholderia type VI secretion system 5. PloS one 12 (10) e0185715
Whiteley, Liam; Haug, Maria; Klein, Kristina; Willmann, Matthias; Bohn, Erwin; Chiantia, Salvatore; Schwarz, Sandra
(See online at https://doi.org/10.1371/journal.pone.0185715)
