Leptospirosis is a worldwide zoonotic disease that is caused by spirochetes in the genus Leptospira. Thisdisease is now regarded as one of the important emerging infectious diseases worldwide, with the latestoutbreaks occurring in Nicaragua, Brazil, India, Malaysia, Thailand and the United States. The clinicalmanifestations of leptospirosis are varied, ranging from a relatively mild flu-like illness to a severe syndromeof multi-organ infection that is associated with a high mortality. The ultimate goal of the proposed research isto increase our understanding of the basic biology and genetic differences between pathogenic and nonpathogenicstrains of Leptospira, employing a range of genome based technologies. The specific hypothesisbehind this proposal is that strains of Leptospira have major genetic differences that may be associated withtheir ability to cause disease, and that the pathogenic species alter the expression of appropriate genes inorder to cope with the changes encountered in the environment. As such, we aim to increase ourunderstaning of species diversity of different strains of Leptospira employing comparative genomehybridization techniques, and to understand the regulatory network(s) controlling gene expression that allowLeptospira species to sense and adapt to growth as either a parasitic or free-living organism.
The SpecificAims are also designed to study the interaction between Leptospira and its host by monitoring the genomewidechanges in leptospiral gene expression upon contact with host cells and to identify and characterizegenes that are differentially expressed during host-pathogen interaction.An increased understanding of Leptospira biology will present opportunities to develop methods to addressthis pathogen, and will also serve as a model to understand the basic biology and pathogenic potential ofemerging pathogenic species.
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