Open AccessComparative genomic view of mechanisms of variation in Neisseria meningitidis through sequencing and analysis of a third meningococcal genome from serogroup C strain FAM18
Author(s) -
Stephen D. Bentley,
George Vernikos,
Lori Snyder,
Carol Churcher,
C. Arrowsmith,
Tracey Chillingworth,
Ann Cronin,
Paul H. Davis,
Nancy Holroyd,
Kay Jagels,
Mark Maddison,
Sharon Moule,
Ester Rabbinowitsch,
Sarah Sharp,
Louise Unwin,
Sally Whitehead,
Michael A. Quail,
Mark Achtman,
Bart Barrell,
Nigel J. Saunders,
Julian Parkhill
Publication year - 2005
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.0030023.eor
Subject(s) - neisseria meningitidis , biology , genetics , genome , strain (injury) , meningococcal disease , whole genome sequencing , microbiology and biotechnology , virology , computational biology , gene , bacteria , anatomy
The bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus