Journal of Biosciences

, Volume 41, Issue 1, pp 13–19 | Cite as

Phase variation of Opa proteins of Neisseria meningitidis and the effects of bacterial transformation

  • Manish Sadarangani
  • J Claire Hoe
  • Katherine Makepeace
  • Peter van der Ley
  • Andrew J Pollard
Brief communication

Abstract

Opa proteins are major proteins involved in meningococcal colonization of the nasopharynx and immune interactions. Opa proteins undergo phase variation (PV) due to the presence of the 5′-CTCTT-3′ coding repeat (CR) sequence. The dynamics of PV of meningococcal Opa proteins is unknown. Opa PV, including the effect of transformation on PV, was assessed using a panel of Opa-deficient strains of Neisseria meningitidis. Analysis of Opa expression from UK disease-causing isolates was undertaken. Different opa genes demonstrated variable rates of PV, between 6.4 ×10–4 and 6.9 ×10–3 per cell per generation. opa genes with a longer CR tract had a higher rate of PV (r 2=0.77, p=0.1212). Bacterial transformation resulted in a 180-fold increase in PV rate. The majority of opa genes in UK disease isolates (315/463, 68.0%) were in the ‘on’ phase, suggesting the importance of Opa proteins during invasive disease. These data provide valuable information for the first time regarding meningococcal Opa PV. The presence of Opa PV in meningococcal populations and high expression of Opa among invasive strains likely indicates the importance of this protein in bacterial colonization in the human nasopharynx. These findings have potential implications for development of vaccines derived from meningococcal outer membranes.

Keywords

Colonization meningococcus Opa protein phase variation transformation 

Notes

Acknowledgements

This study was funded by Action Medical Research through a Research Training Fellowship awarded to MS (RTF1263) and supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the Department of Health’s National Institute of Health Research Biomedical Research Centres funding scheme. This publication made use of the Meningitis Research Foundation Meningococcus Genome Library ( http://www.meningitis.org/research/genome ) developed by Public Health England, the Wellcome Trust Sanger Institute and the University of Oxford as a collaboration with funding from the Meningitis Research Foundation.

AJP is a Jenner Institute Investigator and James Martin Senior Fellow. AJP was previously named as an inventor on a patent for the use of Opa proteins in meningococcal vaccines. AJP has previously conducted clinical trials of meningococcal vaccines on behalf of the University of Oxford, but receives no personal payments from them. AJP is chair of the UK Department of Health’s Joint Committee on Vaccines and Immunisation and chair of the European Medicine Agency’s Scientific Advisory Group on Vaccines. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. Other authors have no conflicts of interest.

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Copyright information

© Indian Academy of Sciences 2016

Authors and Affiliations

  • Manish Sadarangani
    • 1
  • J Claire Hoe
    • 1
  • Katherine Makepeace
    • 1
  • Peter van der Ley
    • 2
  • Andrew J Pollard
    • 1
  1. 1.Oxford Vaccine Group, Department of PaediatricsUniversity of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, Churchill HospitalOxfordUK
  2. 2.Institute for Translational VaccinologyBilthovenThe Netherlands

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