Investigation of the binding of virulence factors of important infectious pathogens with proinflammatory lipid molecules: Establishment of a novel mechanism of pathogen’s evasion of host defense and Search for new targets for therapeutic development

The proposed multi-disciplinary research initiative falls in line with the University Strategic research theme of "Infection and Immunology". The success of this research plan will lay the molecular and structural foundation for delineating the role of virulence factors found in many intracellular pathogens and characterizing their binding with lipids, which is a largely unchartered property of these virulence factors. Improved knowledge in these subject areas will shed light on the host-pathogen interactions of these intracellular pathogens, including how they can exploit host lipids, how they can survive within the macrophage niche of the host and how they can evade the host immunity defense. Our characterization of their interaction with lipid molecules by cell-based and cell-free methods will provide important molecular and structural information to guide the structure-based screening of inhibitors against these virulence factors. The list of hit compounds produced will be useful leads for research to develop new and better chemotherapeutic intervention to combat multi-drug resistant bacteria, which is a growing threat both locally and globally. This project is supported by a a GRF grant titled "Investigation of the binding of cell wall proteins of Penicillium marneffei and Aspergillus fumigates with proinflammatory lipid signaling molecules: A mechanism of pathogen’s evasion of host defense?" (GRF765312M)