Abstract
Based on chromosome sequences, the human pathogen Borrelia miyamotoi phylogenetically clusters with species that cause relapsing fever. But atypically for relapsing fever agents, B. miyamotoi is transmitted not by soft ticks but by hard ticks, which also are vectors of Lyme disease Borrelia species. To further assess the relationships of B. miyamotoi to species that cause relapsing fever, I investigated extrachromosomal sequences of a North American strain with specific attention on plasmid-borne vsp and vlp genes, which are the underpinnings of antigenic variation during relapsing fever. For a hybrid approach to achieve assemblies that spanned more than one of the paralogous vsp and vlp genes, a database of short-reads from next-generation sequencing was supplemented with long-reads obtained with real-time DNA sequencing from single polymerase molecules. This yielded three contigs of 31, 16, and 11 kb, which each contained multiple and diverse sequences that were homologous to vsp and vlp genes of the relapsing fever agent B. hermsii. Two plasmid fragments had coding sequences for plasmid partition proteins that differed from each other from paralogous proteins for the megaplasmid and a small plasmid of B. miyamotoi. One of 4 vsp genes, vsp1, was present at two loci, one of which was downstream of a candiate prokaryotic promoter. A limited RNA-seq analysis of a population growing in the blood of mice indicated that of the 4 different vsp genes vsp1 was the one that was expressed. The findings indicate that B. miyamotoi has at least four types of plasmids, two or more of which bear vsp and vlp gene sequences that are as numerous and diverse as those of relapsing fever Borrelia. The database and insights from these findings provide a foundation for further investigations of the immune responses to this pathogen and of the capability of B. miyamotoi for antigenic variation.
Highlights
Borrelia miyamotoi is a host-associated spirochete that is transmitted between its mammalian reservoirs by ticks of the genus Ixodes Its vectors include I. scapularis in eastern North America, I. pacificus in far-western North America, I. ricinus in Europe, and I. persulcatus in Russia and Asia
These included coding sequences for PF32 or ParA proteins, PF49 proteins, and PF50 proteins, as well as “Open reading frames (ORFs)-A” coding sequences that were commonly found in association with genes for partitioning proteins of plasmids [35, 42]
Did this study establish that antigen variation occurs during B. miyamotoi infection? No This will likely require the demonstration of evasion of adaptive immunity by a switch of surface proteins during an experimental infection with a minimum infectious inoculum of a clonal population and attribution of that switch to a reversible DNA rearrangement [57]
Summary
Borrelia miyamotoi is a host-associated spirochete that is transmitted between its mammalian reservoirs by ticks of the genus Ixodes (reviewed in [1, 2]) Its vectors include I. scapularis in eastern North America, I. pacificus in far-western North America, I. ricinus in Europe, and I. persulcatus in Russia and Asia. These species are the vectors of the Lyme disease agents of the genus Borrelia, as well as other zoonotic pathogens, like Anaplasma phagocytophilum and Babesia microti, in the same areas where B. miyamotoi is enzootic. B. miyamotoi’s disposition for neuroinvasion was illustrated by cases of meningoencephaliltis in patients with pre-existing immunodeficiences [16, 17]
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