Assembly of the type III secretion system in enteropathogenic E. coli and C. rodentium

Pathogenic E. coli bacteria cause severe intestinal infection and diarrhea in humans, leading to millions of cases of infection every year. The virulence of pathogenic E. coli and many other gram-negative bacterial pathogens (a bacteria type characterized by its membrane structure) is determined by the type III secretion systems (TTSS). TTSS are multi-protein macromolecular “machines” that mediate the secretion and translocation of bacterial proteins into the cytoplasm of eukaryotic cells – a key step in causing infection. Most of the 20 unique structural components constituting this secretion system are highly conserved among animal and plant pathogens and are also evolutionarily related to proteins in the flagellar-specific export system, another protein secretion system that has been extensively studied. However, real hard biochemical analysis of TTSS has not been done. Dr. Hendrikje Oldehinkel is investigating how the TTSS is built and how it works. She is dissecting protein to protein interactions and assembly of the type III secretion apparatus in enteropathogenic E.coli and in a mouse pathogen, Citrobacter rodentium. Her work employs a combination of biochemical techniques: electroforesis, immunoblotting, stable isotope labelling, mass spectrometry and electron microscopy. Oldehinkel’s research will contribute to the understanding of the structure of TTSS and the role the components of the type III secretion system play in the architecture and function of the system. Understanding TTSS is important for finding new therapeutic options against not only gram-negative bacterial pathogens, but also against many other disease-causing pathogens.