Understanding meningococcal disease: studying patient genomes and their disease causing bacteria

Understanding meningococcal disease by simultaneously studying genetic blueprints of patients and the meningococci causing their illness

Researchers
Dr Shamez Ladhani, Dr Mary Ramsay, Prof Ray Borrow, Prof Martin Maiden, Prof Christoph Tang.
Start Date
01 Jun 2017
Category
Prevention
Organisation
Public Health England, London, UK, Public Health England, Manchester, UK, University of Oxford, Oxford, UK.

What is this project about?

This project provides a unique opportunity for the genomes of patients to be linked together with the genomes of the meningococci that caused disease. This will be a unique database of human-bacteria genome pairs that will allow investigators to study interactions at an individual level and relate them to clinical disease and outcomes. 

The research team will examine genetic sequences for variations in critical genes, initially focusing on the human complement system and the respective meningococcal binding proteins which have been identified as major risk factors, as well as any novel interactions that could potentially have implications for next generation meningococcal vaccines.

Aims

  • To develop a unique anonymised database with individual level data linking whole genome sequences from patients with laboratory confirmed invasive meningococcal disease with clinical course of illness and whole genome sequences from the responsible meningococci (PHE)
  • To analyse the whole genome human and meningococcal data pairs to better understand critical interactions at a genetic level (PHE)
  • To visualise potential interactions through computer modelling (University of Oxford)

Why is it important?


Although large scale genetic studies involving several thousand patients with meningococcal disease have already been performed and important genetic markers have been identified that make some people more susceptible to this deadly infection, it is clear that we are only studying half the picture. In order to truly understand how humans interact with bacteria, we need to study the genetic blueprint of patients with meningococcal disease alongside the genetic blueprint of the particular bacterium that cause their illness. Together with the clinical information collected by PHE through national surveillance, these researchers will create a single database that will become an invaluable resource for decades to come.

Potential outcomes

In the short term, the team will develop a unique database for researchers around the world that will contain whole genome data for individual patient-meningococcus pairs, alongside important clinical data. 

Other studies have already identified individual variations in the human genome, mainly in genes encoding parts of the immune system, that are linked to disease outcome. Using the database, the team will investigate how these genetic variations lead to changes in the way they interact with their meningococcal counterparts. 

Continuing advances in information technology should also allow more complex analyses to be performed, such as looking for genetic variations along whole pathways rather than restricting to specific genes that code for individual proteins.

As the meningococcal B vaccine is introduced, the database will also include any cases of MenB disease in children who have already been vaccinated, allowing invaluable insight into how the vaccine works and why vaccine failure has occurred. 

In the longer term, the preliminary genomic analyses performed will allow for further work on interactions between bacteria and the people they infect, potentially enabling new vaccine targets to be identified.

Generous donation from the Jessica Bethell Charitable Foundation

The Jessica Bethell Charitable Foundation has very generously donated a further £30,000 to Meningitis Research Foundation to be put towards this research project that aims to better understand meningococcal meningitis and septicaemia. 

A cheque for that amount was presented to Professor Ray Borrow, one of the study investigators, at the Manchester Research Laboratories on Friday 11 August 2017. This latest donation is in addition to a previous donation of £40,000 from the Jessica Bethell Charitable Foundation towards the same project, presented in November 2015. 

James and Sally Bethell’s daughter Jessica sadly died from meningococcal group b meningitis in October 2012, at the age of 24. They have since set up the Jessica Bethell Charitable Foundation and have raised impressive funds for charity in memory of Jessica.

Visit the Jessica Bethell Charitable Foundation

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