Bacterial cell division is recognized by the septin cytoskeleton for restriction by autophagy

Abstract

Septins are cytoskeletal proteins widely recognized for their role in eukaryotic cell division. Septins also assemble into cage-like structures that entrap cytosolic Shigella flexneri targeted to macroautophagy/autophagy. Although the Shigella septin cage was discovered ~10 y ago, how septins recognize Shigella was poorly understood. We found that septins are recruited to regions of micrometer-scale curvature presented by dividing bacterial cells, and cardiolipin (a curvature-specific phospholipid) promotes septin recruitment to these regions. Chemical manipulation of bacteria revealed that following recruitment, septins assemble into cages around growing bacterial cells. Once assembled, septin cages inhibit Shigella cell division by autophagy and fusion with lysosomes. Thus, recognition of dividing bacterial cells by the septin cytoskeleton targets intracellular pathogens to antibacterial autophagy.

Keywords: Autophagy; cardiolipin; cytoskeleton; membrane curvature; mitochondria; septins.

Figure 1.

Bacterial factors required for septin cage entrapment. In actively dividing Shigella, FtsZ assembles into the cytokinetic Z-ring at the bacterial midcell. (a) In the cytosol of infected host cells, Shigella cells grow, and constriction of the Z-ring leads to membrane invagination, and finally bacterial cell division. (b) Septins recognize regions of high curvature at the bacterial cell division site and/or poles, where they bind cardiolipin (CL). Septin cages assemble around growing bacterial cells, and inhibit bacterial cell division via autophagy and fusion with lysosomes.