CFH1b Priming - Chemical re-engineering of lipoteichoic acid (LTA) to decrypt its dynamic interplay with host cell surfaces

Project: Other projectOther internal award

Project Details


Lipoteichoic acid (LTA) is emerging as a major virulence factor of Gram+ bacterial pathogens, initiating host cell responses causing organ failure in sepsis. However, mechanisms underlying the biological effects of LTA, such as its mode of interaction with host cells, remain controversial and need to be addressed to develop new anti-microbial strategies. To tackle this challenge, we propose an interdisciplinary approach combining bioorthogonal chemistry, membrane biology and cutting-edge single-molecule imaging that will provide a new way of addressing these biological mechanisms. We initially validated the use of a new fluorescent tool with comparable cellular activity to purified LTA, and which exposed unexpected attachment behaviour at the surface of host cells. Our proof-of-principle CFH proposal builds on these findings, with a study where we will chemically re-engineer LTA to generate trifunctional probes bearing fluorophores, affinity handles, and photoreactive crosslinkers to identify and track the cause of this behavior.
Effective start/end date1/04/181/09/18