<i>Listeria monocytogenes</i> cell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria.

Abstract

<i>Listeria monocytogenes</i> hijacks host actin to promote its intracellular motility and intercellular spread. While <i>L. monocytogenes</i> virulence hinges on cell-to-cell spread, little is known about the dynamics of bacterial spread in epithelia at a population level. Here, we use live microscopy and statistical modeling to demonstrate that <i>L. monocytogenes</i> cell-to-cell spread proceeds anisotropically in an epithelial monolayer in culture. We show that boundaries of infection foci are irregular and dominated by rare pioneer bacteria that spread farther than the rest. We extend our quantitative model for bacterial spread to show that heterogeneous spreading behavior can improve the chances of creating a persistent <i>L. monocytogenes</i> infection in an actively extruding epithelium. Thus, our results indicate that <i>L. monocytogenes</i> cell-to-cell spread is heterogeneous, and that rare pioneer bacteria determine the frontier of infection foci and may promote bacterial infection persistence in dynamic epithelia. This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).