exl, an exchangeable genetic island in Neisseria meningitidis

The genetic structure and evolution of a novel exchangeable meningococcal g enomic island was defined for the important human pathogen Neisseria mening itidis, In 125 meningococcal strains tested, one of three unrelated nucleot ide sequences, designated exl (exchangeable locus), was found between a gen e required for heme utilization, hemO, and col, encoding a putative Escheri chia coli collagenase homologue. The 5' boundary of each exl cassette was t he stop codon of hemO, whereas the 3' boundary was delineated by a 33-bp re peat containing neisserial uptake sequences located downstream of col. One of the three alternative exl cassettes contained the meningococcal hemoglob in receptor gene, hmbR (exl3), In other meningococcal strains, hmbR was abs ent from the genome and was replaced by either a nucleotide sequence contai ning a novel open reading frame, exl2, or a cassette containing exl3. The p roteins encoded by exl2 and exl3 had no significant amino acid homology to HmbR but contained six motifs that are also present in the lipoprotein comp onents of the lactoferrin (LbpB), transferrin (TbpB), and hemoglobin-haptog lobin (HpuA) uptake systems. To determine the evolutionary relationships am ong meningococci carrying hmbR, exl2, or exl3, isolates representing 92 ele ctrophoretic types were examined. hmbR was found throughout the population structure of N. meningitidis (genetic distance, >0.425), whereas exl2 and e xl3 were found in clonal groups at genetic distances of <0.2. The commensal neisserial species were identified as reservoirs for all of the exl casset tes found in meningococci. The structure of these cassettes and their corre lation with clonal groups emphasize the extensive gene pool and frequent ho rizontal DNA transfer events that contribute to the evolution and virulence of N. meningitidis.