PROJECT SUMMARYEnvironmental sensing is at the basis of an organism?s ability to adapt its physiology to respond to changes inits niche. Over the past years, it has emerged that bacteria not only perceive and respond to chemical stimuli,but are capable of sensing and processing physical forces as an environmental cue. In the case of bacterialpathogens, we and others have shown that mechanical stimuli can act as a hallmark of host colonization andlead to activation of virulence genes. Despite this realisation, our mechanistic understanding of pathways andsystems involved in mechanosensing, transduction and processing of physical forces is currently limited, as isour knowledge regarding the role of mechanoregulation within the host environment. The objective here is tounderstand how enterohemorrhagic E. coli, an important human pathogen, responds to physical force. In thehuman host, ingestion of EHEC can lead to enterocolitis and severe complications such as haemolytic uremicsyndrome. These hallmarks of infection are caused by the concerted action of virulence factors, includingcolonization factors and Shiga-like toxins. Here, we will (a) characterize how virulence gene induction respondsto physical forces, (b) determine the biochemical basis of signal transduction between membrane andtranscriptional regulator, and (c) define the role of mechanosensing during the transitions between environmentaland host-associated lifestyles. This work will reveal how EHEC perceive and process physical forces, andintegrate these cues to coordinate their infection cycle. Such knowledge may highlight new targets for thedevelopment of anti-infective strategies that disable the pathogen by rendering it ?numb? to the host.