Martin Maiden on the Population Biology & Molecular Epidemiology of Meningococci
Special Topic of Meningitis Interview, September 2010
And the story of clearing up that mess is the subject of your top paper, with Kate Dingle as lead author (Dingle KE, et al., "Multilocus sequence typing system for Campylobacter jejuni," J. Clin. Microbiol. 39: 14-23, 2001).
C. jejuni is a major cause of human food poisoning by bacteria globally, and the gastroenteritis it causes has a major economic impact. Attempts to type Campylobacter by using serology did not work. The bacterium is a bit like meningococcus in the sense that it can exchange DNA readily. This paper explains how we ported over our MLST system to this organism. The scheme for Campylobacter described in this paper is now the gold standard for typing, which is why it is highly cited.
Sequence-based typing can be used for a variety of investigations. For example, in Campylobacter we used it for disease attribution, identifying the source of infection as retail poultry meat. We are very interested in applying the fundamental biology to healthcare interventions, in this case to reduce food poisoning.
The second paper in this analysis takes up the theme of using sequence typing for epidemiology (Urwin R, Maiden MCJ, "Multi-locus sequence typing: a tool for global epidemiology," Trends Microbiol. 11: 479-87, 2003).
Yes. This paper is authored jointly with Rachel Urwin, who did her Ph.D. with us, working on meningococci. I was lucky that she came with me to Oxford to found the group. This paper describes how MLST can be used as a molecular tool for studying epidemiology on a global scale.
"Some regard our approach as rather eccentric, but in my view it's no more controversial than using mouse models to study human immunity."
An important feature of MLST schemes is that it does not matter when or where you do the typing. It is reproducible, in contrast to many other typing schemes. Here we show how to link ideas from population biology and genetics to practical epidemiology.
The striking feature of your 2002 Lancet paper (Maiden MCJ, Stuart JM, "Carriage of serogroup C meningococci 1 year after meningococcal C conjugate polysaccharide vaccination," 359: 1829-30, 2002), which is a study of the effectiveness of vaccines, is the sheer size of the sample. What influence did this paper have on public health issues?
In 1999 the UK was the first country to introduce meningococcal serogroup C conjugate vaccines, which gives long-term protection. With MLST it was possible to identify the epidemic clone. The UK health authorities took the bold step of introducing the vaccine earlier than they had planned. Our task was to see the population effects of this introduction.
This paper describes the first stage of a very large carriage study involving 16,583 students who had been vaccinated, and demonstrated a herd immunity effect: a vaccine offered to individuals protected the herd. It was an influential paper because health authorities outside the UK were starting to consider when and how to use the vaccine.
A paper from the Journal of Clinical Microbiology in 2000 gives the results from an earlier carriage study concerning meningococci in the Czech Republic (Jolley KA, et al., "Carried meningococci in the Czech Republic: A diverse recombining population," 38: 4492-8, 2000). What's the story here?
Shortly before coming to Oxford I started collaborating with Sunetra Gupta on strain theory. We needed longitudinal data from asymptomatic carriage to test our ideas on the dynamics of the bacterial population but appropriate isolates did not exist in most countries.
Paula Kriz in the Czech Republic had suitable collections and we started a program to characterize them with sequencing techniques. We established a collection of Czech isolates where we had both invasive and carried isolates from equivalent samples.
This paper was influential both in what it told us about meningococci but also as a motivation for other groups studying carried and invasive samples for other pathogens.
Finally Professor Maiden, how would you summarize the results of this selection of papers?
We now have a good understanding about the population structure of meningococci and how it influences disease. What's significant about that is we've also established how the population structure relates to phenotypes, such as the ability to cause disease.
We've been able to show that certain genotypes are much more likely to cause disease than others. That enables the next really exciting phase of study, which is to try to tease out which genetic determinants are important. That's where being able to analyze whole genomes and to correlate the genetic changes in those genomes with well defined isolate collections where the phenotypes are defined, which is where a lot of genetic studies fall down. This is basic, fundamental, science.
In terms of molecular epidemiology, another area Keith Jolley and I have worked on, it's enabled us to develop tools to track disease and take measures to deal with that. Finally, this work is contributing to the design of vaccines.
Professor Martin C. J. Maiden, B.Sc., Ph.D.
Department of Zoology
University of Oxford
Oxford, UK
Martin Maiden MOST CURRENT MOST-CITED PAPER IN ESSENTIAL SCIENCE INDICATORS:
Stackebrandt E, et al., "Report of the ad hoc committee for the re-evaluation of the species definition in bacteriology," Int. J. Syst. Evol. Microbiol. 52: 1043-7, Part 3, May 2002 with 486 cites. Source: Essential Science Indicators from Thomson Reuters.
KEYWORDS: NEISSERIA MENINGITIDIS, NUCLEOTIDE SEQUENCING, POPULATION BIOLOGY, EVOLUTION, PATHOGENIC BACTERIA, COMPARATIVE SEQUENCE ANALYSIS, MENINGOCOCCAL SURFACE PROTEINS, MENINGOCOCCAL SEPTICEMIA, SEROGROUPS, CAPSULAR POLYSACCHARIDES, VIRULENCE, MOLECULAR EPIDEMIOLOGY, CAMPYLOBACTER JEJUNI, MULTILOCUS SEQUENCE TYPING, MLST, STRAIN THEORY, PHENOTYPES, WHOLE GENOMES, VACCINES.