The biologic role of a majority of the Neisseria meningitidis 2100 predicted coding regions is still to be assigned or
experimentally confirmed. Determining the phenotypic effect of gene disruption being a fundamental approach
to understanding gene function, we used high-density signature-tagged transposon mutagenesis, followed by a
large-scale sequencing of the transposon insertion sites, to construct a genome-wide collection of mutants. The
sequencing results for the first half of the 4548 mutants composing the library suggested that we have
mutations in 80%–90% of N. meningitidis nonessential genes. This was confirmed by a whole-genome
identification of the genes required for resistance to complement-mediated lysis, a key to meningococcal
virulence. We show that all the genes we identified, including four previously uncharacterized, were important
for the synthesis of the polysialic acid capsule or the lipooligosaccharide (LOS), suggesting that these are likely
to be the only meningococcal attributes necessary for serum resistance. Our work provides a valuable and
lasting resource that may lead to a global map of gene function in N. meningitidis.