Proximity biotinylation at the host-Shigella interface reveals UFMylation as an antibacterial pathway
TL;DR
A proximity biotinylation approach coupled to quantitative mass spectrometry that maps the host-bacterial interface during infection identifies UFMylation as an ancient antibacterial pathway and holds great promise to reveal other cell-autonomous immunity mechanisms.
Abstract
Host cells contest invasion by intracellular bacterial pathogens with multiple strategies that recognise and/or damage the bacterial surface. To identify host defence factors targeted to intracellular bacteria, we developed a proximity biotinylation approach coupled to quantitative mass spectrometry that maps the host-bacterial interface during infection. Using this method, we discovered that intracellular Shigella and Salmonella become targeted by UFM1-protein ligase 1 (UFL1), an E3 ligase that catalyses the covalent attachment of Ubiquitin-fold modifier 1 (UFM1) to target substrates in a process called UFMylation. Shigella antagonises UFMylation in a dual manner: first, using its lipopolysaccharide to shield from UFL1 recruitment; second, preventing UFM1 decoration by the bacterial effector IpaH9.8. Absence of UFMylation leads to an increase of bacterial burden in human cells and zebrafish larvae. Contrary to ubiquitylation, the protective role of UFMylation is independent of autophagy. Altogether, our proximity mapping of the host-bacterial interface identifies UFMylation as an ancient antibacterial pathway and holds great promise to reveal other cell-autonomous immunity mechanisms.
