Abstract
Many bacterial pathogens require a type 3 secretion system (T3SS) to establish a niche. Host contact activates bacterial T3SS assembly of a translocon pore in the host plasma membrane. Following pore formation, the T3SS docks onto the translocon pore. Docking establishes a continuous passage that enables the translocation of virulence proteins, effectors, into the host cytosol. Here we investigate the contribution of actin polymerization to T3SS-mediated translocation. Using the T3SS model organism Shigella flexneri, we show that actin polymerization is required for assembling the translocon pore in an open conformation, thereby enabling effector translocation. Opening of the pore channel is associated with a conformational change to the pore, which is dependent upon actin polymerization and a coiled-coil domain in the pore protein IpaC. Analysis of an IpaC mutant that is defective in ruffle formation shows that actin polymerization-dependent pore opening is distinct from the previously described actin polymerization-dependent ruffles that are required for bacterial internalization. Moreover, actin polymerization is not required for other pore functions, including docking or pore protein insertion into the plasma membrane. Thus, activation of the T3SS is a multilayered process in which host signals are sensed by the translocon pore leading to the activation of effector translocation.
Highlights
Type 3 secretion systems (T3SSs) are essential virulence factors of more than 30 gram-negative bacterial pathogens [1,2]
We demonstrate that actin polymerization is necessary to convert T3SS pores into an open conformation that is competent for virulence protein delivery
We find that activation of type 3 secretion proceeds in a multistep process whereby bacteria dock onto the translocon pore and activate secretion and delivery of virulence proteins
Summary
Type 3 secretion systems (T3SSs) are essential virulence factors of more than 30 gram-negative bacterial pathogens [1,2]. Contact of the tip complex with the eukaryotic membrane induces the delivery and insertion of two bacterial proteins into the plasma membrane [11,15] that assemble into a heterooligomeric pore known as the translocon pore [16,17,18,19,20]. The T3SS needle and tip complex stably associate with the translocon pore in a process known as docking [21,22,23]. Docking establishes a continuous channel from the bacterial cytoplasm to the eukaryotic cytosol and enables the direct delivery of bacterial effectors into the host cytosol. For several pathogens, including S. flexneri, Y. pseudotuberculosis, and enterohemorrhagic E. coli, efficient T3SS effector translocation depends on host actin polymerization [25,26,27,28,29,30,31]. Whereas the bacterial proteins that induce actin polymerization are known [30,31,32], how actin polymerization contributes to effector protein translocation is unclear
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