The Influence of IS1301 in the Capsule Biosynthesis Locus on Meningococcal Carriage and Disease

Previously we have shown that insertion of IS1301 in the sia/ctr intergenic region (IGR) of serogroup C Neisseria meningitidis (MenC) isolates from Spain confers increased resistance against complement-mediated killing. Here we investigate the significance of IS1301 in the same location in N. meningitidis isolates from the UK. PCR and sequencing was used to screen a collection of more than 1500 meningococcal carriage and disease isolates from the UK for the presence of IS1301 in the IGR. IS1301 was not identified in the IGR among vaccine failure strains but was frequently found in serogroup B isolates (MenB) from clonal complex 269 (cc269). Almost all IS1301 insertions in cc269 were associated with novel polymorphisms, and did not change capsule expression or resistance to human complement. After excluding sequence types (STs) distant from the central genotype within cc269, there was no significant difference for the presence of IS1301 in the IGR of carriage isolates compared to disease isolates. Isolates with insertion of IS1301 in the IGR are not responsible for MenC disease in UK vaccine failures. Novel polymorphisms associated with IS1301 in the IGR of UK MenB isolates do not lead to the resistance phenotype seen for IS1301 in the IGR of MenC isolates.

[1]  M. Pizza,et al.  Characterization of fHbp, nhba (gna2132), nadA, porA, Sequence Type (ST), and Genomic Presence of IS1301 in Group B Meningococcal ST269 Clonal Complex Isolates from England and Wales , 2009, Journal of Clinical Microbiology.

[2]  J. Derrick,et al.  Epidemiological evidence for the role of the hemoglobin receptor, hmbR, in meningococcal virulence. , 2009, The Journal of infectious diseases.

[3]  N. McCarthy,et al.  Association of a Bacteriophage with Meningococcal Disease in Young Adults , 2008, PloS one.

[4]  Bridget Gollan,et al.  Generic mechanisms in neisseria meningitidis for resistance against complement mediated killing , 2008 .

[5]  A. Chan,et al.  A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies , 2008, The Journal of experimental medicine.

[6]  M. Maiden,et al.  Molecular epidemiology of meningococcal disease in England and Wales 1975–1995, before the introduction of serogroup C conjugate vaccines , 2008, Microbiology.

[7]  D. Crook,et al.  Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity. , 2008, The Journal of infectious diseases.

[8]  N. Andrews,et al.  Clinical and immunologic risk factors for meningococcal C conjugate vaccine failure in the United Kingdom. , 2006, The Journal of infectious diseases.

[9]  Malcolm Guiver,et al.  Epidemiology of meningococcal disease in England and Wales 1993/94 to 2003/04: contribution and experiences of the Meningococcal Reference Unit. , 2006, Journal of medical microbiology.

[10]  D. Huson,et al.  Application of phylogenetic networks in evolutionary studies. , 2006, Molecular biology and evolution.

[11]  S. Clarke,et al.  Increased Genetic Diversity of Neisseria meningitidis Isolates after the Introduction of Meningococcal Serogroup C Polysaccharide Conjugate Vaccines , 2005, Journal of Clinical Microbiology.

[12]  K. Jolley,et al.  A chromosomally integrated bacteriophage in invasive meningococci , 2005, The Journal of experimental medicine.

[13]  D. Caugant,et al.  Neisseria meningitidis: an overview of the carriage state. , 2004, Journal of medical microbiology.

[14]  Elizabeth Miller,et al.  Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction , 2004, The Lancet.

[15]  N. Andrews,et al.  Validation of Serological Correlate of Protection for Meningococcal C Conjugate Vaccine by Using Efficacy Estimates from Postlicensure Surveillance in England , 2003, Clinical Diagnostic Laboratory Immunology.

[16]  S. Busby,et al.  The Escherichia coli cAMP receptor protein bound at a single target can activate transcription initiation at divergent promoters: a systematic study that exploits new promoter probe plasmids. , 2002, The Biochemical journal.

[17]  E. Miller,et al.  Impact of meningococcal C conjugate vaccine in the UK. , 2002, Journal of medical microbiology.

[18]  M. Maiden,et al.  Carriage of serogroup C meningococci 1 year after meningococcal C conjugate polysaccharide vaccination , 2002, The Lancet.

[19]  M. Ramsay,et al.  Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story. , 2001, Vaccine.

[20]  N. Andrews,et al.  Efficacy of meningococcal serogroup C conjugate vaccine in teenagers and toddlers in England , 2001, The Lancet.

[21]  M. Achtman,et al.  Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Ahn,et al.  Expression of sialic acid and polysialic acid in serogroup B Neisseria meningitidis: divergent transcription of biosynthesis and transport operons through a common promoter region , 1996, Journal of bacteriology.

[23]  S. Hammerschmidt,et al.  Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element. , 1996, The EMBO journal.

[24]  P. Magnus,et al.  Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population , 1994, Journal of clinical microbiology.

[25]  K. Cartwright,et al.  The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica , 1987, Epidemiology and Infection.

[26]  M. Artenstein,et al.  HUMAN IMMUNITY TO THE MENINGOCOCCUS , 1969, The Journal of experimental medicine.

[27]  M. Ramsay,et al.  Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines. , 2007, FEMS microbiology reviews.

[28]  M. Frosch,et al.  Analysis of transcriptional control mechanisms of capsule expression in Neisseria meningitidis. , 2001, International journal of medical microbiology : IJMM.

[29]  Jeffrey H. Miller.  Experiments in molecular genetics , 1972 .