A novel mutagenesis technique provides urgently needed information about the pathogenesis of meningococcal meningitis. In November's Nature Medicine (6, 1269–1274, 2000), Christopher Tang and colleagues report the use of signature tagged mutagenesis (STM) to identify genes required for Neisseria meningitides virulence. Tang and his team modified N. meningitides DNA in vitro using the transposon Tn10. The pathogens incorporate exogenous DNA into their genome through homologous recombination, allowing efficient uptake and integration of modified alleles. Screening for mutants that were unable to infect the bloodstream of neonatal rats led to the identification of 73 genes, only eight of which were previously associated with pathogenicity. “The novelty of this work is that the insertional mutagenesis was carried out in vitro, overcoming limitations imposed by currently available tools for the genetic manipulation of N. meningitides” says bacteriologist Ian Feavers of the National Institute for Biological Standards and Control (UK). The results provide the first comprehensive analysis of the genes involved in meningococcal meningitis and may lead to new vaccines/therapeutics.