Aptamers Against FliC_Jimenez,Guillermo

The Clinical Advantages of Aptamer Research for Melioidosis on the B. pseudomallei Surface Protein FliC
by Guillermo Jimenez

Abstract

            Melioidosis is a bacterial infection prominent in the Southeast Asian tropical region of the world. It is caused by the illusive Burkholderia pseudomallei. Modern techniques for diagnosing the disease have encountered several obstacles due to the bacterium’s ability of prolonged incubation within the host. Many patients succumb to the infection’s lethal symptoms before they are diagnosed in time to be administered the proper treatment. An aptamer against B. pseudomallei would be utilized to rapidly diagnose Melioidosis before the bacteria has any time to metastasize throughout the infected host. More specifically, an aptamer against FliC, a motor protein present in the flagellum of the organism, could effectively be radiolabeled to localize the infection in the body.

            FliC, also known as flagellin, is a critical motor protein present in the flagella of B.pseudomallei. It interacts with the structure of the entire organelle, forming filaments from thin organized strands (Matzke, 2003). With a known molecular weight of 39 kDa the protein monomer functions as a multimer in full length, giving the flagellum a whip-like characteristic that propels the bacterium forward (Winsor, 2008). Such is so, that an aptamer may also be used to block the binding site of the protein to the rest of the bacterium, essentially immobolizing the organism preventing its proliferation into full-blown Melioidosis. However, such a technique is yet to be tested and little is known about the protein’s affinity for nucleic acid molecules. The SELEX process of in vitro selection of such an aptamer against the protein has already commenced with one initial round. FliC is being provided by Dr. Katy Brown of the University of Texas’ Institute for Cellular and Molecular Biology and her laboratory. Thus..

Specific Aim 1: To identify an aptamer against FliC target.

Specific Aim 2: To localize FliC by incorporating an aptamer into modern diagnostic techniques of Melioidosis.

Specific Aim 3 (speculated): Utilize the aptamer as an inhibitory molecule in the formation of B.pseudomallei’s flagellum, thereby incapacitating its movement.

Full proposal

Progress Report

Target Progress Report 2

Target Final Report