Speaker Dr Effie Bastounis, Junior Group Leader, Interfaculty Institute for Microbiology and Infection Medicine (IMIT), Eberhard Karls University & University Hospital Tübingen, Germany

Title ERK activation waves coordinate mechanical cell competition leading to collective onslaught of bacterially-infected cells

Host Jody Rosenblatt

 

Abstract Epithelial cells respond to infection by the intracellular bacterial pathogen Listeria monocytogenes by altering their mechanics and promoting collective infected cell extrusion (CICE), which limits infection spread across cell monolayers. Here, using in vitro (epithelial monolayers) and in vivo (zebrafish larvae) models infected with L. monocytogenes or Shigella flexneri, we explored how biochemical signaling, and in particular extracellular signal-regulated kinase (ERK) activity waves, coordinate the mechanical battle between infected and surrounder uninfected cells that leads to CICE. We discover that when ERK waves are suppressed, alterations in cell shape and kinematics associated with CICE are abolished, and cells behave like quiescent uninfected monolayers. In absence of ERK waves, uninfected cells surrounding infection foci are unable to polarize and reinforce their monolayer stresses and promote CICE. The findings I will present reveal that crosstalk between ERK waves and cell mechanics is key for collective elimination of large domains of infected cells. We propose that ERK waves serve as a spatial alarm signal propagating across cell monolayers to modulate their biomechanics, thus enabling fast coordinated action against the threat of infection spread.