Overview
Approximately 1- 3% of the proteins in bacteria are lipoproteins, which are characterized by a post-translationally attached lipid moiety. These lipoproteins attach to cell membranes through their lipid chain and play key roles in various physiological processes, including nutrient uptake, cell signaling, and host-pathogen interactions. Previous research on lipoprotein maturation primarily in the model bacterium Escherichia coli (E. coli) has revealed that lipoproteins are synthesized in the cytoplasm and undergo maturation at the inner membrane (IM) through the sequential action of three enzymes. Initially, phosphatidyl-glycerol:prolipoprotein diacylglyceryl transferase (Lgt) recognizes the N-terminal signal peptide and attaches a diacylglycerol group from phospholipids to the sulfhydryl group of the invariant cysteine within the C-terminal
region of the signal peptide. This is followed by Signal peptidase II (SPase II), which cleaves the signal peptide, resulting in S-diacylglyceryl-cysteine becoming the new N-terminus. Finally, the apolipoprotein N-acyltransferase (Lnt) acylates the amino group of cysteine, producing a triacylated N-acyl S-diacylglyceryl-lipoprotein. Once lipoproteins exit the maturation pathway, they are directed to specific subcellular locations. In diderm bacteria, lipoproteins can remain in the inner membrane (IM) or be shuttled to the outer membrane (OM). Importantly, bacterial lipoproteins are morphologically and chemically distinct from the similarly named human lipoproteins, which are particles of non-covalently attached lipids and proteins that travel in the human bloodstream.
Research Area 1: Study of the structure and function of Borrelia burgdorferi lipoproteins
Lyme disease is a tick-borne illness caused by spirochetes belonging to members of the Borrelia sensu lato group, which includes Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. This disease is common in North America and Europe, with an estimated 476,000 cases diagnosed and treated per year in the US and over 200,000 cases per year in western Europe. Current treatments involve the use of antibiotics in the early stages of infection. However, Lyme disease can often progress without diagnosis, leading to serious long-term conditions. Therefore, to combat the growing threat from B. burgdorferi, novel therapies are urgently needed.
The genome of B. burgdorferi is predicted to encode 127 lipoproteins, which tether to membranes via covalently-attached lipids. These lipoproteins are either retained at the IM or trafficked to the OM where they perform their location-specific functions. Surface-exposed OM lipoproteins are of particular interest since they mediate interactions with their environment and are accessible to the immune system. These lipoproteins have been shown to play key roles in nutrient acquisition,immune evasion, and host-pathogen interactions. To help identify potential therapeutic targets, we study the structure and function of lipoproteins using bioinformatic, biochemical, and biophysical tools.
Research area 2: Developing novel lipoprotein-based biomaterials
Lipid-based nanoparticles are a highly promising technology that uses lipids to create various materials, including liposomes, solid lipid nanoparticles, and lipid-polymer hybrid nanoparticles. One advantage of these materials over inorganic nanoparticles is their biocompatibility. These materials are easily absorbed and metabolized in the human body, resulting in less toxic degradation products. Because lipoproteins contain both a lipid moiety and a protein domain, we believe that lipoproteins can be used to create novel biomaterials. Our lab aims to investigate the design potential of bacterial lipoproteins for the development of novel therapeutics.
