Structural characterization and inhibitor design of sialyltransfersases involved in lipooligosaccharide biosynthesis of Gram-negative pathogens

Bacterial resistance to antibiotics has become a major challenge in drug development. It is thus necessary to develop novel antimicrobial therapies to combat bacterial infection. Such development would require a thorough understanding of the mechanisms bacteria employ to cause disease. Campylobacter bacteria is the most commonly reported foodborne pathogen that cause acute gastroenteritis (inflammation of the stomach and intestines) and diarrheal illness in developed countries. Almost 99% of the reported cases are caused by a specific strain, called C. jejuni. Sialic acid (sugar molecules) on the cell surface of C. jejuni mimics human gangliosides and thus camouflages the bacteria from the host immune system. Cecilia Chiu is investigating the three-dimensional molecular structure of sialyltranferases, the class of enzymes responsible for the transfer of sialic acids onto the surface of Campylobacter. Cecilia aims to understand the mechanism of these enzymes and to develop molecules that inhibit the enzymes from sialylating the bacterial cell surface. This research could ultimately lead to the development of new therapeutic inhibitors against this common human pathogen.