Abstract

In an effort to understand how a tick-borne pathogen adapts to the body louse, we sequenced and compared the genomes of the recurrent fever agents Borrelia recurrentis and B. duttonii. The 1,242,163–1,574,910-bp fragmented genomes of B. recurrentis and B. duttonii contain a unique 23-kb linear plasmid. This linear plasmid exhibits a large polyT track within the promoter region of an intact variable large protein gene and a telomere resolvase that is unique to Borrelia. The genome content is characterized by several repeat families, including antigenic lipoproteins. B. recurrentis exhibited a 20.4% genome size reduction and appeared to be a strain of B. duttonii, with a decaying genome, possibly due to the accumulation of genomic errors induced by the loss of recA and mutS. Accompanying this were increases in the number of impaired genes and a reduction in coding capacity, including surface-exposed lipoproteins and putative virulence factors. Analysis of the reconstructed ancestral sequence compared to B. duttonii and B. recurrentis was consistent with the accelerated evolution observed in B. recurrentis. Vector specialization of louse-borne pathogens responsible for major epidemics was associated with rapid genome reduction. The correlation between gene loss and increased virulence of B. recurrentis parallels that of Rickettsia prowazekii, with both species being genomic subsets of less-virulent strains.

Highlights

  • Spirochetes of the genus Borrelia are bacterial pathogens responsible for relapsing fever and Lyme borreliosis

  • Whereas the Lyme disease agents Borrelia burgdorferi [1,2], Borrelia garinii [3], and Borrelia afzelii [4] are transmitted by hard ticks, the numerous relapsing fever borreliae are typically transmitted by soft ticks

  • We show that the genomic content of B. recurrentis is a subset of that of B. duttonii, the genes of which are undergoing a decay process

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Summary

Introduction

Spirochetes of the genus Borrelia are bacterial pathogens responsible for relapsing fever and Lyme borreliosis. Tick-borne relapsing fever borreliae, including Borrelia duttonii, have shown extended vectorial capacity, whereas transmission of Borrelia recurrentis, which causes louse-borne relapsing fever, is restricted to Pediculus humanus [5,6]. Besides their mode of transmission, these two highly related species of Borrelia exhibit very different epidemiological and clinical features. B. recurrentis, once responsible for worldwide outbreaks, is currently limited to Ethiopia and its surrounding countries [8] It causes fewer relapses, but spontaneous mortality remains as high as 2–4% despite antibiotics, with patients suffering from distinctive hemorrhagic syndrome [9]. B. recurrentis and other louseborne pathogens, including the typhus agent Rickettsia prowazekii [11] and the trench fever agent Bartonella quintana [12], exhibit higher virulence than their respective tick-borne relatives B. duttonii, Rickettsia conorii [13], and Bartonella henselae [12]

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