Funded Projects

Human cohort studies have uncovered a link between the microbiota and major depressive disorder (MDD). Inflammation and microbial infection can also elicit delirium and other forms of cognitive impairment. However, few investigators combine infection research with behavior and cognitive assessments in suitable model organisms, which has hindered discovery of the underlying mechanisms of microbe-induced cognitive impairment. We propose to combine our unique expertise in microbial pathogenesis and the molecular and behavioral basis of psychiatric disorders to develop an experimental approach for assessing microbe-induced cognitive impairment. We propose three small pilot projects to establish preliminary data for future grant proposals that represent a substantial departure from each PI’s currently funded research. In project 1, we will establish a protocol for monitoring cognitive function in rats after gut colonization by a control organism (Escherichia coli) compared to each of two constituents of the microbiota that have been associated with MDD (Morganella morganii and Klebsiella aerogenes). In Project 2, we aim to monitor cognitive function during inflammation induced by cryptococcal capsular polysaccharide in the CNS, which accumulates and persists in the CNS of patients after sterilization by antifungal therapy and can lead to a post-infection inflammatory syndrome. In Project 3, we aim to establish a protocol for monitoring cognitive function after acute urinary infection (UTI). Confusion and delirium are the most common indicators of suspected UTI in older adults; we will establish acute UTI with Escherichia coli, the most common cause of UTI, as well as Klebsiella pneumoniae, an organism that is associated with a higher incidence of delirium during UTI. Completion of these projects will facilitate investigation of the host and microbial factors that drive infection-induced delirium and cognitive impairment and may inform clinical assessments in patients.