Investigation of the PhoPQ system and nucleotide biosynthesis as targets for inhibition of Salmonella Typhimurium biofilm formation.

Important human pathogens become (multi-)resistant to currently availabe antibiotics, urging the need for alternative anti-bacterical treatments. Biofilms are surface-associated communities of bacteria, embedded in a self-produced slime layer. The importance of biofilms becomes clear from the fact that they are involved in 80% of all infections and occur widespread in the environment. Bacteria in biofilms are up to 1000-fold more resistant to antibiotics, disinfectants and host immune systems and are an important obstacle in the eradication of bacterial infections and bacterial contamination in industrial settings. As such, interference with biofilm formation is a promising alternative anti-bacterial strategy. Salmonella is a major foodborne pathogen, causing about 1.3 billion infections every year. The spread of Salmonella is largely due to the fact that Salmonella is able to form biobilms on different surfaces such as plants, intestinal tissue, gallstones and industrial and sanitary installations. The goal of this project is the further exploration and optimization of inhibitors of Salmonella biofilms, identified during my Ph.D. This includes a detailed study of (i) the molecular targets of the biofilm inhibitors (PhoPQ-system and nucleotide biosynthesis), (ii) the interaction of the biofilm inhibitors with these targets and (iii) the identification of new inhibitors affecting the same targets.

Keywords:Salmonella, Interference with biofilm formation, Biofilm inhibitor, Alternative anti-bacterial treatment, PhoPQ, Nucleotide biosynthesis, Biofilm formation

Disciplines:Plant biology