Neural Dysfunction Following Francisella tularensis Infection

Abstract

Abstract Francisella tularensis is a gram-negative intracellular coccobacillus that is the causative agent of tularemia. Local, acute inflammation is beneficial since it can clear bacterial infections, remove cellular damage and promote the healing of tissue. However, F. tularensis is capable of bypassing the immune system and causing an overactivation of inflammation, known as a “cytokine storm”. This cytokine storm increases host cell damage, nutrient availability and serves an immune distraction allowing the bacterium to replicate. Other infections that cause cytokine storms include ebola, pandemic influenza, hantavirus, and HIV, all BSL3 pathogens. The routes of transmission for F. tularensis are many and intertwined. Infection could be the result of inhaling air droplets containing infectious bacteria, coming into direct contact with an infected animal or being bitten by an infected arthropod such as a tick, flea or mosquito. Eating and drinking contaminated meat and water can also lead to infection and different disease manifestations occur depending on the route of transmission. While extensive research has documented infection of the spleen, liver and lung, there hasn’t been any reports of F. tularensis productively infecting the brain, until now. This work focuses on characterizing the effects of F. tularensis infection of the brain. We hypothesize that damage caused by F. tularensis neural infection will have a negative effect on behavior. This work aims to identify these negative effects based on the anatomical location of the bacteria foci, regions containing numerous bacteria. With the use of brain mapping and behavioral assays, we seek to determine the impact of F. tularensis infection on behavior and cognition.