Abstract

Despite the increasing popularity of multilocus sequence typing (MLST), the most appropriate method for characterizing bacterial variation and facilitating epidemiological investigations remains a matter of debate. Here, we propose that different typing schemes should be compared on the basis of their power to infer clonal relationships and investigate the utility of sequence data for genealogical reconstruction by exploiting new statistical tools and data from 20 housekeeping loci for 93 isolates of the bacterial pathogen Neisseria meningitidis. Our analysis demonstrated that all but one of the hyperinvasive isolates established by multilocus enzyme electrophoresis and MLST were grouped into one of six genealogical lineages, each of which contained substantial variation. Due to the confounding effect of recombination, evolutionary relationships among these lineages remained unclear, even using 20 loci. Analyses of the seven loci in the standard MLST scheme using the same methods reproduced this classification, but were unable to support finer inferences concerning the relationships between the members within each complex.

Highlights

  • The demonstration that some bacterial pathogen populations are structured into lineages that differ in their propensity to cause disease represents a major achievement of molecular epidemiology (Musser, 1996)

  • The 20-locus analysis was, able to identify a large number of additional younger clades as well as some older clades (Fig. 5). This partially filled the gap in the overall distribution of ages for the reconstructed clades with that expected in a neutrally evolving population, the youngest and oldest subdivisions remained unresolved (Fig. 5). These analyses demonstrate that the clonal complex concept captures an appreciable proportion of the information on genealogical relationships amongst N. meningitidis isolates available from the seven-locus multilocus sequence typing (MLST) scheme

  • The seven-locus MLST data do not provide information on longer timescales, and the interrelationships among the lineages corresponding to clonal complexes remain unresolved, even with 20-locus data

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Summary

Introduction

The demonstration that some bacterial pathogen populations are structured into lineages that differ in their propensity to cause disease represents a major achievement of molecular epidemiology (Musser, 1996). Public health interventions can be targeted at particular lineages, as achieved with strainspecific meningococcal vaccines deployed in several countries (Jodar et al, 2002). Such interventions should avoid changing the ecology of the meningococcus in ways that might favour the spread of vaccine escape variants or more invasive genotypes that would increase the overall disease burden (Maiden & Spratt, 1999). This population structuring enables genetic differences between invasive and non-invasive meningo-

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