Entrapment of Intracytosolic Bacteria by Septin Cage-like Structures

Abstract

Actin-based motility is used by various pathogens for dissemination within and between cells. Yet host factors restricting this process have not been identified. Septins are GTP-binding proteins that assemble as filaments and are essential for cell division. However, their role during interphase has remained elusive. Here, we report that septin assemblies are recruited to different bacteria that polymerize actin. We observed that intracytosolic Shigella either become compartmentalized in septin cage-like structures or form actin tails. Inactivation of septin caging increases the number of Shigella with actin tails and enhances cell-to-cell spread. TNF-α, a host cytokine produced upon Shigella infection, stimulates septin caging and restricts actin tail formation and cell-to-cell spread. Finally, we show that septin cages entrap bacteria targeted to autophagy. Together, these results reveal an unsuspected mechanism of host defense that restricts dissemination of invasive pathogens.

Septin assemblies form by diffusion-driven annealing on membranes

“…In vivo, septin assembly is restricted both in time and in space through local activation of small GTPases such as Cdc42. Localized signaling leads to higher-order septin structures forming closely apposed to the plasma membrane at the plane of division, sites of polarity, and curved membranes (10,(12)(13)(14). Notably, eukaryotic cells of different geometries build higher-order septin assemblies of various shapes, sizes, and functions (4, 15, 16).…”

“…Septin function is required for cell division and viability in many eukaryotes whereas misregulation is associated with cancers and neurodegenerative disorders (5)(6)(7)(8). Furthermore, septins mediate entry of both bacterial and fungal pathogens into host cells (9)(10)(11). In vivo, septin assembly is restricted both in time and in space through local activation of small GTPases such as Cdc42.…”

How the Study of Listeria Monocytogenes has Led to New Concepts in Biology

“…Septins can also entrap Shigella into cage-like structures that restrict cell-to-cell spread and therefore dissemination of the bacteria [81]. In the case of L. monocytogenes, no efficient septin caging has been observed, but the above-reported studies indicate that septins play a role as scaffold for protein recruitment in several biological processes, including host-pathogens interactions.…”

“…In addition to be recruited at the site of bacterial entry, septin rings assemble around both L. monocytogenes and S. flexneri actin comet tails, suggesting that septin recruitment is a general pattern wherever actin polymerisation is taking place [81]. Septins can also entrap Shigella into cage-like structures that restrict cell-to-cell spread and therefore dissemination of the bacteria [81].…”

The Inside Story of Shigella Invasion of Intestinal Epithelial Cells

“…For Shigella, autophagy is associated with rings of septins, described as molecular scaffolds implicated in cell division (Mostowy et al 2010). Septins form "cages" entrapping Shigella, preventing intracellular motility and targeting bacteria to autophagy.…”