Use of lipid A as therapeutic and diagnostic.

ABSTRACT: Lipid A is the membrane anchor for Gram-negative bacteria that holds the much larger lipopolysaccharide (LPS) molecule in place in the outer membrane. Recently, we reported its use along with related molecules from Gram + and fungal organisms to identify microbes direct from source. Importantly in mammals, Toll receptor 4 (TLR4) recognizes lipid A the result of which is activation of a cytokine cascade that can aid the host in clearing the infection or if unchecked lead to a deadly cytokine storm. There are a range of activities from agnostic to antagonistic that are directly related to structure. To exploit this we are working to better define the lipid A structure activity relationship (SAR) for use as a vaccine adjuvants and antisepsis therapeutics. Part of this work involves study of macrophage proteome changes induced by agonistic and antagonistic lipid A reagents as well as modeling the software SILCS to identity key components of lipid A’s interaction with TLR4.