Our overarching goal is to understand how the inflammatory mediator extracellular ATP (eATP) regulates infection and inflammation in the gut. We have a holistic approach studying both the host and the microbes. We focus on Shigella flexneri and Escherichia coli with non-pathogenic as well as pathogenic lifestyles.

Infectious diseases are major killers worldwide. Diarrhoeal diseases in particular show high morbidity and mortality in developing countries, mostly in the elderly and young children, in which they are responsible for delays in growth and cognitive development.

To combat infection, our body mounts a protective immune response. However, in inflammatory diseases this response is dysregulated and can cause great harm. We urgently need a deep understanding of immune mechanisms to harness their protective powers during infection and prevent uncontrolled inflammation with specific therapy.

ATP has many essential functions inside cells, but outside cells ATP acts as signalling molecules in higher and lower eukaryotes. Importantly, eATP is the archetypical Danger Associated Molecular Pattern (DAMP) and regulates stress and damage responses during sterile inflammation (that is, inflammation in the absence of infection).

We discovered that eATP is a key mediator during infection. In fact, intestinal epithelial cells secrete ATP as early alert signal during infection with S. flexneri, enteropathogenic E. coli, and Salmonella enterica, which provokes acute inflammation in the gut.

We run an ambitious programme to understand how intestinal cells and bacteria regulate the abundance of and respond to eATP in the gut.

We recently discovered that the mechanosensor PIEZO1 detects bacterial invasion of intestinal epithelial cells and triggers ATP secretion as well as immune gene expression. Further, we discovered that members of the Enterobacteriaceae are able to respond to eATP by reprogramming their transcriptional and metabolic landscapes, which modifies sensitivity to antimicrobials and virulence gene expression.

In addition, we study mechanisms of pathogenesis in S. flexneri at genome-wide level. Newly identified fitness factors may serve as targets for specific antibacterial drugs in a pathogen globally showing ever increasing incidence of antibiotic resistance.