Studies to elucidate the binding capacities of Enterotoxigenic Escherichia coli (ETEC) colonisation factor fimbriae to human glycans
In this project we are glyco-engineering CHO-K1 cell lines to study human small intestinal glycan/ETEC CF fimbriae binding interactions. In parallel to this work, we are also using molecular docking to identify novel glycan binding sites on ETEC CF fimbriae, as well as aid our understanding of why these intestinal/ETEC CF interactions may occur.
This project is funded by the Swedish Research Council (framework grants: 2013-6615 and 2011-3435).
Participants: Prof. Ann-Mari Svennerholm (PI) and Dr Lynda Mottram, Dep. of Microbiology and Immunology in collaboration with Prof. Jan Holgersson, Dep. of Clinical Chemistry and Transfusion Medicine and Sonali Chavan (PhD student), Dep. of Chemistry and Molecular Biology.
Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhoea related illness in infants and young children as well as travellers to ETEC endemic countries. The rise of multidrug resistance against such a pathogen can be attributed to the widespread and indiscriminate use of chemotherapeutic agents in these enteric disease endemic countries. As an infection prerequisite, ETEC bind to the host’s small intestine using adhesions such as colonisation factor (CF) fimbriae. Subsequently, ETEC CF fimbriae are prerequisites for the initiation of ETEC pathogenesis and represent a critical point at which ETEC infections could be prevented. Despite this the human intestinal binding receptor(s) for ETEC CFs, remain less well defined. In this project we are glyco-engineering CHO-K1 cell lines to study human small intestinal glycan/ETEC CF fimbriae binding interactions. In parallel to this work, we are also using molecular docking to identify novel glycan binding sites on ETEC CF fimbriae, as well as aid our understanding of why these intestinal/ETEC CF interactions may occur. The subsequent findings from these studies could lead to a better molecular understanding of ETEC pathogenesis, aiding in the development of vaccines and/or non-antibiotic therapeutics.