The Human-Specific miR-6762-5p Is an Activator of RhoA GTPase Enhancing Shigella flexneri Intercellular Spreading

Abstract

MicroRNAs have recently emerged as major players in host –bacterial pathogen interactions, either as part of the host defense mechanism to neutralize infection or as a bacterial arsenal aimed at subverting host cell functions. Here, we identify the newly evolved human microRNA miR-6762-5p as a new player in the host–Shigella interplay. A microarray analysis in infected epithelial cells allowed the detection of this miRNA exclusively during the late phase of infection. Conditional expression of miR-6762-5p combined with a transcriptome analysis indicated a role in cytoskeleton remodeling. Likewise, miR-6762-5p enhanced stress fiber formation through RhoA activation, and in silico analysis identified several regulators of RhoA activity as potential direct transcriptional targets. We further showed that miR-6762-5p expression induces an increase in Shigella intercellular spreading, while miR-6762-5p inhibition reduced bacterial dissemination. We propose a model in which the expression of miR-6762-5p induces cytoskeleton modifications through RhoA activation to achieve a successful dissemination of Shigella in the host.