January 1, 2010.
Tularemia, also known as rabbit fever, is an infectious disease caused by the gram-negative bacterium Francisella tularensis. Transmission to animals and humans occurs via several routes, including ingestion of contaminated water, or inhalation of contaminated dusts or aerosols, tick bites, and skin contact with infected animals. Because of its highly pathogenic and opportunistic nature, F. tularensis is a likely candidate for use as an airborne biological weapon. For this reason, developing a vaccine and identifying appropriate treatments are critical to effective bioterrorism preparedness and response. It may exist in nature within encysted amoeba, which may represent a similar survival strategy within human macrophages. To facilitate antimicrobial drug development, a study of the encystment process was carried out. One of the proteins discovered during this study was Rep 24, a novel Francisella cysteine protease. In this current study the interaction between Rep 24 and a possible interactive substrate, JPM-565, is observed. This interaction is detected through the optical sensing technique known as Dual Polarization Interferometry (DPI). Immobilized Rep 24 is layered on a thiol chip, followed by a wash of JPM. Changes in the refractive index of the molecules, as measured by DPI, demonstrate binding events between the two. Data from binding experiments are later used for quantitative measurements of size, density and mass. Future work includes investigation of additional Francisella tularensis proteins and screens against small molecules that may bind and abrogate function, leading to countermeasures against Francisella tularensis.
Lawrence Livermore National Laboratory (LLNL)