Dottorato in BIOLOGIA CELLULARE E DELLO SVILUPPO

Titolo della tesi: Role of multidrug resistance efflux pumps during intracellular life of Adherent-Invasive Escherichia coli strain LF82

Efflux pumps (EPs) are inner membrane proteins found in all organisms, from bacteria to humans, and are involved in the transport process of the cell. EPs mediate the transport of many types of molecules and contribute to the development of multidrug resistance (MDR) thanks to their ability to transport simultaneously different antibiotics. To date an increasing number of works, indicate that, besides their role in the antibiotics transport, MDR EPs play an important role in several cellular functions such as biofilm formation, stress response, maintenance of cellular homeostasis and detoxification of cell from metabolic intermediates. They also actively contribute to the bacterial interaction with plant and animal cells, and to the virulence of many pathogenic bacteria. This let us to consider their role in the intracellular life of our model system, LF82, the prototype strain of Adherent Invasive Escherichia coli (AIEC). AIEC is a group of enteropathogenic E. coli, capable of colonizing the ileal mucosa of patients with Crohn's disease (CD) causing strong intestinal inflammation through a sophisticated infectious strategy. Indeed, AIEC strains are able to invade and replicate in epithelial cells and macrophages, where they replicate extensively in large vacuoles without inducing apoptosis. The aim of my PhD thesis was to analyze the expression profile of the genes encoding the MDR EPs present in the LF82 genome during macrophage and epithelial cell infection in order to identify which MDR EPs were relevant during the survival within host cells or in the early stages of the invasive process. The data I obtained demonstrates for the first time that MDR EPs are involved in the invasive process and contribute to the intracellular life of AIEC strains and open new perspectives in the study of AIEC interactions with host cells