Abstract
SummaryThe cytoskeleton occupies a central role in cellular immunity by promoting bacterial sensing and antibacterial functions. Septins are cytoskeletal proteins implicated in various cellular processes, including cell division. Septins also assemble into cage-like structures that entrap cytosolic Shigella, yet how septins recognize bacteria is poorly understood. Here, we discover that septins are recruited to regions of micron-scale membrane curvature upon invasion and division by a variety of bacterial species. Cardiolipin, a curvature-specific phospholipid, promotes septin recruitment to highly curved membranes of Shigella, and bacterial mutants lacking cardiolipin exhibit less septin cage entrapment. Chemically inhibiting cell separation to prolong membrane curvature or reducing Shigella cell growth respectively increases and decreases septin cage formation. Once formed, septin cages inhibit Shigella cell division upon recruitment of autophagic and lysosomal machinery. Thus, recognition of dividing bacterial cells by the septin cytoskeleton is a powerful mechanism to restrict the proliferation of intracellular bacterial pathogens.
Highlights
Septins are highly conserved filament-forming proteins that play key roles in eukaryotic cell division (Mostowy and Cossart, 2012; Saarikangas and Barral, 2011)
We examined the recruitment of SEPT6-GFP to Shigella M90T mCherry using time-lapse microscopy
We observed that for 87.4% ± 1.9% of entrapped bacteria, septins are first recruited to the division site and/or the cell poles before they assemble into cage-like structures (Figures 1A and 1B; Video S1), suggesting a role for bacterial curvature in septin recruitment
Summary
Septins are highly conserved filament-forming proteins that play key roles in eukaryotic cell division (Mostowy and Cossart, 2012; Saarikangas and Barral, 2011). Discovered for their role in division of budding yeast (Hartwell, 1971), recent work has shown that septins play a role in division of mitochondria (Pagliuso et al, 2016; Sirianni et al, 2016). It has been shown that $50% of entrapped bacteria are metabolically inactive (Sirianni et al, 2016), but their fate is mostly unknown
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