RNAi screen reveals a role for PACSIN2 and caveolins during bacterial cell-to-cell spread

Abstract

Listeria monocytogenes is a human bacterial pathogen that disseminates through host tissues using a process called cell-to-cell spread. This critical yet understudied virulence strategy resembles a vesicular form of intercellular trafficking that allows L. monocytogenes to move between host cells without escaping the cell. Interestingly, eukaryotic cells can also directly exchange cellular components via intercellular communication pathways (e.g. trans-endocytosis) using cell-cell adhesion, membrane trafficking, and membrane remodeling proteins. Therefore, we hypothesized that L. monocytogenes would hijack these types of host proteins during spread. Using a focused RNAi screen, we identified 22 host genes that are important for L. monocytogenes spread. We then found that caveolins (CAV1 and CAV2) and the membrane sculpting F-BAR protein PACSIN2 promote L. monocytogenes protrusion engulfment during spread, and that PACSIN2 specifically localized to protrusions. Overall, our study demonstrates that host intercellular communication pathways may be co-opted during bacterial spread and that specific trafficking and membrane remodeling proteins promote bacterial protrusion resolution.\n\nSummaryThe human bacterial pathogen Listeria monocytogenes disseminates through host tissues using a process called cell-to-cell spread. In this study, Sanderlin et al., discover that host proteins that normally regulate membrane trafficking and membrane remodeling in uninfected settings are also co-opted by Listeria to promote spread.