Comparative population genomics of the Borrelia burgdorferi species complex reveals high degree of genetic isolation among species and underscores benefits and constraints to studying intra-specific epidemiological processes.

Maude Jacquot,David Abrial,Xavier Bailly,Valérie Choumet,Martine Garnier,Jocelyn De Goër,Nelly Dorr,Alexandre Claude,Gwenaël Vourc'H,Natacha Sertour,Patrick Gasqui,Benjamin Faure,Elisabeth Ferquel,Myriam Charras-Garrido,Mathieu Gonnet

doi:10.1371/journal.pone.0094384

Abstract

Lyme borreliosis, one of the most frequently contracted zoonotic diseases in the Northern Hemisphere, is caused by bacteria belonging to different genetic groups within the Borrelia burgdorferi species complex, which are transmitted by ticks among various wildlife reservoirs, such as small mammals and birds. These features make the Borrelia burgdorferi species complex an attractive biological model that can be used to study the diversification and the epidemiology of endemic bacterial pathogens. We investigated the potential of population genomic approaches to study these processes. Sixty-three strains belonging to three species within the Borrelia burgdorferi complex were isolated from questing ticks in Alsace (France), a region where Lyme disease is highly endemic. We first aimed to characterize the degree of genetic isolation among the species sampled. Phylogenetic and coalescent-based analyses revealed clear delineations: there was a ∼50 fold difference between intra-specific and inter-specific recombination rates. We then investigated whether the population genomic data contained information of epidemiological relevance. In phylogenies inferred using most of the genome, conspecific strains did not cluster in clades. These results raise questions about the relevance of different strategies when investigating pathogen epidemiology. For instance, here, both classical analytic approaches and phylodynamic simulations suggested that population sizes and migration rates were higher in B. garinii populations, which are normally associated with birds, than in B. burgdorferi s.s. populations. The phylogenetic analyses of the infection-related ospC gene and its flanking region provided additional support for this finding. Traces of recombination among the B. burgdorferi s.s. lineages and lineages associated with small mammals were found, suggesting that they shared the same hosts. Altogether, these results provide baseline evidence that can be used to formulate hypotheses regarding the host range of B. burgdorferi lineages based on population genomic data.

Highlights

Zoonotic diseases caused by pathogens that are transmitted among different host species represent an emergent threat for human health [1]
Given that the levels of linkage disequilibrium in B. burgdorferi s.s. and B. garinii in our regional sample were higher than those calculated for the global sample, we investigated the extent of geographical isolation within each species by using single nucleotide polymorphisms (SNPs) frequencies to analyze the distribution of HST values between our two sampling sites (Table 2, Figure 6)
Distribution of diversity among species of the Borrelia burgdorferi complex We studied species delineations within the B. burgdorferi complex using genomic data from sympatric isolates and geographically independent reference sequences

Summary

Introduction

Zoonotic diseases caused by pathogens that are transmitted among different host species represent an emergent threat for human health [1]. In vector-borne systems, in which infected vectors feed on and transmit the pathogen to several hosts, it is possible to characterize pathogen diversity using population genomic studies. These studies, which use information obtained from the genome of pathogens isolated from questing vectors, offer researchers the opportunity to indirectly study the spread of pathogens within and among host communities. Housekeeping genes, which are involved in basic cell cycle and metabolic functions, are mostly subject to purifying selective pressures [3] They are more likely to contain relevant information about gene flow among pathogen populations and other demographic events, especially if pathogen lineages have had the opportunity to recombine [4]. One of the main challenges of population genomic approaches is to integrate hypotheses about patterns of diversity that are observed at the scale of individual genes or genome regions into evolutionary scenarios that are coherent at the level of the whole genome

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