Functional genomics of Neisseria meningitidis pathogenesis

The pathogenic bacterium Neisseria meningitidis is an important cause of se pticemia and meningitis, especially in childhood(1). The establishment and maintenance of bacteremic infection is a prerequisite for all the pathologi cal sequelae of meningococcal infection. To further understand the genetic basis of this essential step in pathogenesis, we analyzed a library of 2,85 0 insertional mutants of N. meningitidis for their capacity to cause system ic infection in an infant rat model. The library was constructed by in vitr o modification of Neisseria genomic DNA with the purified components of Tn1 0 transposition(2). We identified 73 genes in the N. meningitidis genome th at are essential for bacteremic disease. Eight insertions were in genes enc oding known pathogenicity factors. Involvement of the remaining 65 genes in meningocoocal pathogenesis has not been demonstrated previously, and the i dentification of these genes provides insights into the pathogenic mechanis ms that underlie meningococcal infection. Our results provide a genome-wide analysis of the attributes of N, meningitidis required for disseminated in fection, and may lead to new interventions to prevent and treat meningococc al infection.