The Propensity of Different Borrelia burgdorferi sensu stricto Genotypes to Cause Disseminated Infections in Humans

Dykhuizen, Daniel E.; Sandigursky, Sabina; Nadelman, Robert B.; Nowakowski, John; Brisson, Dustin; Wormser, Gary P.; Schwartz, Ira

doi:10.4269/ajtmh.2008.78.806

Cited by 111 publications

(116 citation statements)

References 25 publications

(39 reference statements)

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“…However, transport of B. burgdorferi between northeastern and midwestern I. scapularis populations appears to be relatively infrequent. Regional isolation of B. burgdorferi genotypes may have epidemiological implications due to differences in clinical outcomes associated with specific genotypes (51)(52)(53)(54)(55).…”

Section: Resultsmentioning

confidence: 99%

Phylogeography of Borrelia burgdorferi in the eastern United States reflects multiple independent Lyme disease emergence events

Hoen

Margos

Bent

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

149

179

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Since its first description in coastal Connecticut in 1976, both the incidence of Lyme disease and the geographic extent of endemic areas in the US have increased dramatically. The rapid expansion of Lyme disease into its current distribution in the eastern half of the US has been due to the range expansion of the tick vector, Ixodes scapularis, upon which the causative agent, Borrelia burgdorferi is dependent for transmission to humans. In this study, we examined the phylogeographic population structure of B. burgdorferi throughout the range of I. scapularis-borne Lyme disease using multilocus sequence typing based on bacterial housekeeping genes. We show that B. burgdorferi populations from the Northeast and Midwest are genetically distinct, but phylogenetically related. Our findings provide strong evidence of prehistoric population size expansion and east-to-west radiation of descendent clones from founding sequence types in the Northeast. Estimates of the time scale of divergence of northeastern and midwestern populations suggest that B. burgdorferi was present in these regions of North America many thousands of years before European settlements. We conclude that B. burgdorferi populations have recently reemerged independently out of separate relict foci, where they have persisted since precolonial times.geography ͉ phylogeny ͉ ticks ͉ multilocus sequence typing

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Section: Resultsmentioning

confidence: 99%

Phylogeography of Borrelia burgdorferi in the eastern United States reflects multiple independent Lyme disease emergence events

Hoen

Margos

Bent

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

149

179

View full text Add to dashboard Cite

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“…Third, the severe human virulence of B. burgdorferi s.s. is itself evidence for it being a generalist parasite of mammalian hosts, since despite the fact that humans are not its natural reservoir hosts, B. burgdorferi s.s. is capable of invading and infecting the human tissues. Although B. burgdorferi s.s. strains appear to vary in human virulence (Dykhuizen et al 2008;Wormser et al 2008), it has been argued that associations between human pathogenecity and genomic groups are weak and all groups have the potential to cause invasive infections in humans (Alghaferi et al 2005;Jones et al 2006).…”

Section: Maintenance Of Genome Clusters By Frequency-dependent Selectionmentioning

confidence: 99%

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Vargas²,

et al. 2011

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How genomic diversity within bacterial populations originates and is maintained in the presence of frequent recombination is a central problem in understanding bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, consist of diverse genomic groups co-infecting single individual vertebrate hosts and tick vectors. To understand mechanisms of sympatric genome differentiation in B. burgdorferi, we sequenced and compared 23 genomes representing major genomic groups in North America and Europe. Linkage analysis of .13,500 single-nucleotide polymorphisms revealed pervasive horizontal DNA exchanges. Although three times more frequent than point mutation, recombination is localized and weakly affects genome-wide linkage disequilibrium. We show by computer simulations that, while enhancing population fitness, recombination constrains neutral and adaptive divergence among sympatric genomes through periodic selective sweeps. In contrast, simulations of frequency-dependent selection with recombination produced the observed pattern of a large number of sympatric genomic groups associated with major sequence variations at the selected locus. We conclude that negative frequency-dependent selection targeting a small number of surface-antigen loci (ospC in particular) sufficiently explains the maintenance of sympatric genome diversity in B. burgdorferi without adaptive divergence. We suggest that pervasive recombination makes it less likely for local B. burgdorferi genomic groups to achieve host specialization. B. burgdorferi genomic groups in the northeastern United States are thus best viewed as constituting a single bacterial species, whose generalist nature is a key to its rapid spread and human virulence. G ENETIC discontinuity, the basis of biodiversity, is ubiquitous in prokaryotes as well as in eukaryotes. Most bacterial populations display a highly clonal genetic structure, in which the observable number of multilocus genotypes is far fewer than the number expected under the assumption of free recombination (Maynard Smith et al. 1993). Bacterial clonality was originally thought of as a result of a lack or rarity of recombination among asexually reproducing and independently evolving clones (Ochman and Selander 1984). Since then, molecular surveys of natural bacterial populations using protein electrophoresis, multilocus sequencing typing (MLST), and whole-genome PRJNA3, PRJNA28633, PRJNA19839, PRJNA29359, PRJNA28629, PRJNA29357, PRJNA21003, PRJNA19835, PRJNA28627, PRJNA21001, PRJNA29361, PRJNA28621, PRJNA19837, PRJNA20999, PRJNA28631, PRJNA29363, PRJNA17057, PRJNA19841, PRJNA12554, PRJNA28625, PRJNA29573, PRJNA19843, and PRJNA28635. 1 Present address: Odum School of Ecology, University of Georgia, Athens, GA 30602. sequencing revealed that horizontal genetic exchange is in fact often more frequent than point mutations in bacteria, including species known as strongly clonal (Maynard Smith et al. 1993;Feil and Spratt 2001;Didelot and Maiden 2010;Retc...

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“…2 However, there is large variation in incidence among states where transmission of B. burgdorferi occurs, possibly because of differences in reservoir host ecology, [16][17][18] climate, [19][20][21][22][23] rates of human contact, 13 genetic variation among strains, [23][24][25][26] or differences between states in reporting practices. Thus, relationships between acarological risk and incidence may differ among geographic regions.…”

Section: Introductionmentioning

confidence: 99%

Geographic Variation in the Relationship between Human Lyme Disease Incidence and Density of Infected Host-Seeking Ixodes scapularis Nymphs in the Eastern United States

Pepin¹,

Eisen²,

Mead³

et al. 2012

The American Journal of Tropical Medicine and Hygiene

143

140

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Abstract. Prevention and control of Lyme disease is difficult because of the complex biology of the pathogen's (Borrelia burgdorferi) vector (Ixodes scapularis) and multiple reservoir hosts with varying degrees of competence. Cost-effective implementation of tick-and host-targeted control methods requires an understanding of the relationship between pathogen prevalence in nymphs, nymph abundance, and incidence of human cases of Lyme disease. We quantified the relationship between estimated acarological risk and human incidence using county-level human case data and nymphal prevalence data from field-derived estimates in 36 eastern states. The estimated density of infected nymphs (mDIN) was significantly correlated with human incidence (r = 0.69). The relationship was strongest in highprevalence areas, but it varied by region and state, partly because of the distribution of B. burgdorferi genotypes. More information is needed in several high-prevalence states before DIN can be used for cost-effectiveness analyses.

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The Propensity of Different Borrelia burgdorferi sensu stricto Genotypes to Cause Disseminated Infections in Humans

Cited by 111 publications

References 25 publications

Phylogeography of Borrelia burgdorferi in the eastern United States reflects multiple independent Lyme disease emergence events

Phylogeography of Borrelia burgdorferi in the eastern United States reflects multiple independent Lyme disease emergence events

Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium

Geographic Variation in the Relationship between Human Lyme Disease Incidence and Density of Infected Host-Seeking Ixodes scapularis Nymphs in the Eastern United States

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