The innate immune response is the first line of defence against pathogens, which is initiated by the detection of pathogen-derived signatures referred to as Pathogen-Associated Molecular Patterns (PAMPs). Plants and animals sense PAMPs and in turn differentially regulate a large set of immune response genes, among which microRNAs (miRNAs) were recently identified. In the model plant Arabidopsis thaliana, dozens of miRNAs are PAMP-responsive, among them we found that a conserved miRNA contributes to antibacterial resistance. More recently, we have reported a major role of the Arabidopsis miRNA pathway in antibacterial defence and, as a corollary, have identified a series of bacterial-derived suppressors of the miRNA pathway. This pioneering work represents an important contribution to the understanding of virulence strategies employed by pathogenic bacteria and suggests that analogous strategies may also be used by human pathogenic bacteria.In the proposed project, we will first aim to investigate the extent to which an RNA silencing suppression strategy employed by a phytopathogenic bacterial effector is also used by effectors from human pathogenic bacteria. We will additionally aim to generate a comprehensive view of small RNA repertoires produced in the course of bacterial infection using both a human and a plant pathogenic bacteria. The second aspect of our proposal is directed toward a better understanding of the influence of PAMPs and bacterial effectors on Arabidopsis transcriptional gene silencing (TGS), a pathway that silences transposable elements and repeats through the establishment and maintenance of cytosine DNA methylation. Finally, we will aim to identify and characterize bacterial effectors that interfere with TGS. Overall, these studies should reveal completely novel bacterial virulence strategies and contribute to a better understanding of the mechanisms underlying post-transriptional- and transcriptional- gene silencing in different organisms.