Neutral microepidemic evolution of bacterial pathogens

Abstract

Understanding bacterial population genetics is vital for interpreting the response of bacterial populations to selection pressures such as antibiotic treatment or vaccines targeted at only a subset of strains. The evolution of transmissible bacteria occurs by mutation and localized recombination and is influenced by epidemiological as well as molecular processes. We demonstrate that the observed population genetic structure of three important human pathogens, Streptococcus pneumoniae, Neisseria meningitidis, and Staphylococcus aureus, can be explained by using a simple evolutionary model that is based on neutral mutational drift, modulated by recombination, and which incorporates the impact of epidemic transmission in local populations. The predictions of this neutral ''microepidemic'' model are found to closely fit observed genetic relatedness distributions of bacteria sampled from their natural population, and it provides estimates of the relative rate of recombination that agree well with empirical estimates. The analysis suggests the emergence of neutral bacterial population structure from overlapping microepidemics within clustered host populations and provides insight into the nature and size distribution of these clusters. These findings challenge the assumption that strains of bacterial pathogens differ markedly in relative fitness. infinite-alleles model ͉ multilocus sequence typing ͉ recombination I t is now accepted that bacteria do not conform to the clonal model of evolution (1). The importance of recombination has become increasingly clear in recent years, both as a fundamental process in strain diversification (2) and as a mechanism by which strains acquire virulence factors or resistance determinants (3). Homologous recombination in bacteria involves the replacement of a small segment of the bacterial chromosome (a few kilobases) with the corresponding region from another isolate (2). The frequency of these localized recombinational events may be extremely rare, resulting in species that are highly clonal [e.g., Mycobacterium species (4, 5)], or extremely frequent, resulting in species that are almost completely nonclonal [e.g., Helicobacter pylori (6)]. Consequently, theoretical approaches developed for exclusively sexual or asexual organisms are inappropriate, and, at present, there is no general theory reconciling these variable properties of bacteria. The problem is further complicated by serious sampling biases arising as a result of overrepresentation of disease isolates or antibiotic-resistant isolates in clinical strain collections (1). This problem is especially acute for some species, including Streptococcus pneumoniae, Staphylococcus aureus, and Neisseria meningitidis, which we focus on here and which are ''accidental'' pathogens in that healthy carriage is common, with disease a rare outcome. Finally, the host population structure will influence transmission and needs to be accounted for when considering bacterial population structure: Spread of directly transmitted bacteria within a ...

How clonal are Neisseria species? The epidemic clonality model revisited

“…This hypothesis, which is already debatable when semi/epidemic clonality is concerned, can hardly account for PCE features, in particular the presence of deep phylogenies (12). It should be noted that in the case of N. meningitidis the classical panselectionist hypothesis has been challenged by several authors (12,35,40).…”

Inference of Bacterial Microevolution Using Multilocus Sequence Data

“…The three published estimates of r/u are more consistent, each including 1. These are our estimate (0.7-1.2), the estimate of Jolley et al (2005) (0.16-1.8), and that of Fraser et al (2005) based on the distribution of allele sharing within a population (1.1). For Bacillus, 95% credibility regions for r/m and r/u based on our method are 1.3-2.8 and 0.2-0.5, respectively, showing that recombination is rare compared to the level observed in Neisseria or in many other bacteria.…”

“…A coalescent prior has the advantage of tractability and simplicity. However, it has been shown that for many bacterial populations, there is an excess of isolates with identical allelic profiles, in comparison to neutral expectations (Fraser et al 2005;Jolley et al 2005). Since bacteria do not disperse at each replication, different growth conditions in different physical locations could introduce local correlations in the genealogy.…”

A comparison of homologous recombination rates in bacteria and archaea

“…A wide spectrum of methods exist to estimate this ratio, using either microevolutionary techniques (Falush et al, 2001;Feil et al, 2004) or population genetics methodology (Fearnhead et al, 2005;Fraser et al, 2005;Jolley et al, 2005). The ratio r/y is a measure of the frequency at which recombination occurs relative to mutation and therefore has an intuitive interpretation: if for example r/y ¼ 2, recombination events occur two times as often as point mutation in the evolution of the population.…”