The Genome of Borrelia recurrentis, the Agent of Deadly Louse-Borne Relapsing Fever, Is a Degraded Subset of Tick-Borne Borrelia duttonii

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.

Author Summary

Borreliae are vector-borne spirochetes that are responsible for Lyme disease and recurrent fevers. We completed the genome sequences of the tick-borne Borrelia duttonii and the louse-borne B. recurrentis. The former of these is responsible for emerging infections that mimic malaria in Africa and in travellers, and the latter is responsible for severe recurrent fever in poor African populations. Diagnostic tools for these pathogens remain poor with regard to sensitivity and specificity due, in part, to the lack of genomic sequences. In this study, 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. These phenomena are common to all louse-borne pathogens compared to their tick-borne counterparts. In B. recurrentis, this process may be due to the inactivation of genes encoding DNA repair mechanisms, implying the accumulation of errors in the genome. The increased virulence of B. recurrentis could not be traced back to specific virulence factors, illustrating the lack of correlation between the virulence of a pathogen and so-called virulence genes. Knowledge of these genomes will allow for the development of new molecular tools that provide a more-accurate, sensitive, and specific diagnosis of these emerging infections.