The fate of intracellular EPEC

Infections with enteropathogenic E. coli (EPEC) are a major cause of diarrheal disease in children under the age of three in developing countries. While EPEC are generally considered non-invasive pathogens that bind to the surface of enterocytes of the small intestine and inject effector proteins into host cells via a Type III Secretion System, several early studies provided evidence that EPEC is taken up into the host cell during infection. The uptake process appears to be dependent on the presence of the EPEC adherence factor (EAF) plasmid encoding a type IV pilus that mediates bacterial attachment, and the bacterial outer membrane protein intimin, which is involved in the intimate adhesion of EPEC to the host cell. Studies on the fate of intracellular EPEC and their role during infection are still missing. However, a more thorough understanding of the process is essential for the development of future treatment strategies as an intracellular lifestyle enables bacteria to evade immune responses as well as antibiotic treatment. In preliminary studies, we were able to show that EPEC was taken up into both, HeLa as well as HT-29 cells during infection. Using transmission electron microscopy, we found intracellular bacteria in both, membrane-bound vesicles as well as in the cytosol, suggesting, that the bacteria are able to survive in and escape the pathogen-containing vacuole and thereby lysosomal degradation. In the future, we will assess the ability of EPEC to be taken up into both phagocytic and non-phagocytic cells, determine the fate of EPEC inside host cells, and assess whether intracellular bacteria can survive inside and escape from the cells to cause reinfection.