Neisseria meningitidis is still the major cause of bacterial meningitis and septicemia worldwide. The septic shock caused by Neisserial invasive disease is characterized by the presence of skin lesions (petecchial rashes and purpura). Despite the strong association of meningococcal disease and purpura as well as the serious prognosis associated with it, the bacterial factors and physiological processes underlying these events at molecular and cellular level are still largely undescribed.
Here we propose to use a recently developed humanized-mouse model of meningococcal purpura to study by functional genomics (Transcriptome analysis and gene fitness analysis by High-throuput insertion track sequencing, HITS) the host-bacteria interactions during the process of vascular colonization by N.meningitidis in vivo. We expect that combination of these two approaches would highlight bacterial and host mechanisms important for vascular colonization. By the combination of cellular and biochemical approaches we expect to dissect these mechanisms and elicit bacterial determinants used to colonize and proliferate in human blood vessels and host molecular mechanisms that participates in causing vascular damage and purpura fulminans in response to bacterial infection. Understanding the details of vascular leakage may also give indications as to how N. meningitidis are able to cross the Blood Brain Barrier and cause meningitis.
This experimental approach could have the potential to highlight suitable targets for future innovative meningococcal therapeutics and vaccines development. Futhermore, this project will give to the fellow the opportunity to learn scientific, technical and complementary skills, which could support his career development to become an independent researcher in the field of host-pathogen interactions.
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