Salmonella are motile, gram-negative, pathogens that infect eukaryotic cells. Outbreaks of salmonellosis are a great economic and health problem worldwide. Many bacteria, like Salmonella, swim through liquid environments by rotating a helical organelle, the flagellum. This sophisticated nanomachine is functionally and structurally related to virulence-associated type-III secretion systems (T3SS) of pathogenic bacteria. The ability to move is of crucial importance for Salmonella virulence and infection of eukaryotic cells. Although the importance of bacterial motility and T3S in virulence of Salmonella is established, a detailed understanding of the expression and molecular interplay between the flagellar and virulence systems during infection is missing.
The aim of this research program is to study the mechanisms of bacterial motility during bacteria-host interactions and the molecular function of T3SS using an unique combination of sophisticated bacterial genetics, microscopy, biochemistry and infection biology techniques.
Both flagellar motility and the process of T3S are essential for virulence and represent attractive targets for novel anti-microbial agents. Therefore, I will analyze the general importance of flagella and bacterial motility during the Salmonella infection process (Aim 1). In complementary projects, I will focus on the molecular mechanisms of bacterial T3SS like the mechanism of substrate translocation (Aim 2), and screen for compounds that inhibit T3SS (Aim 3).
The proposed research program will provide novel and fundamental insights into our understanding of the molecular details of Salmonella virulence. Thereby, the initial events required for the commitment of the bacteria to invasive diseases could become clear. Importantly, this knowledge could be used to design specific inhibitors of bacterial T3SS, which might have the potential for new anti-bacterial agents that are urgently needed at a time when antibiotic resistance is increasing.
Fields of science
- natural sciencesbiological sciencesbiochemistry
- natural sciencesbiological sciencesgenetics
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesphysical sciencesopticsmicroscopy
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Call for proposal
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