Dataset Information

Comparative genomics analysis of three conserved plasmid families in the Western Hemisphere soft tick-borne relapsing fever borreliae provides insight into variation in genome structure and antigenic variation systems.

ABSTRACT: Borrelia spirochetes, causative agents of Lyme disease and relapsing fever (RF), have a uniquely complex genome consisting of a linear chromosome and circular and linear plasmids. The plasmids harbor genes important for the vector-host life cycle of these tick-borne bacteria. The role of Lyme disease causing Borrelia plasmids is more refined compared to RF spirochetes because of limited plasmid-resolved genomes for RF spirochetes. We recently addressed this limitation and found that three linear plasmid families (F6, F27, and F28) were syntenic across all species. Given this conservation, we further investigated the three plasmid families. The F6 family, also known as the megaplasmid, contained regions of repetitive DNA. The F27 was the smallest, encoding genes with unknown function. The F28 family encoded the expression locus for antigenic variation in all species except Borrelia hermsii and Borrelia anserina. Taken together, this work provides a foundation for future investigations to identify essential plasmid-localized genes that drive the vector-host life cycle of RF Borrelia .

Importance

Borrelia spp. spirochetes are arthropod-borne bacteria found globally and infect humans and other vertebrates. RF borreliae are understudied and misdiagnosed pathogens because of the vague clinical presentation of disease and the elusive feeding behavior of argasid ticks. Consequently, genomics resources for RF spirochetes have been limited. Analyses of Borrelia plasmids have been challenging because they are often highly fragmented and unassembled. By utilizing Oxford Nanopore Technologies, we recently generated plasmid-resolved genomes for seven Borrelia spp. found in the Western Hemisphere. This current study is a more in-depth investigation into the linear plasmids that were conserved and syntenic across species. This analysis determined differences in genome structure and, importantly, in antigenic variation systems between species. This work is an important step in identifying crucial plasmid-borne genetic elements essential for the life cycle of RF spirochetes.

SUBMITTER: Kneubehl AR

PROVIDER: S-EPMC10028826 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Comparative genomics analysis of three conserved plasmid families in the Western Hemisphere soft tick-borne relapsing fever borreliae provides insight into variation in genome structure and antigenic variation systems.

Kneubehl Alexander R AR Lopez Job E JE

bioRxiv : the preprint server for biology 20230306

<i>Borrelia</i> spirochetes, causative agents of Lyme disease and relapsing fever (RF), have a uniquely complex genome consisting of a linear chromosome and circular and linear plasmids. The plasmids harbor genes important for the vector-host life cycle of these tick-borne bacteria. The role of Lyme disease causing <i>Borrelia</i> plasmids is more refined compared to RF spirochetes because of limited plasmid-resolved genomes for RF spirochetes. We recently addressed this limitation and found tha ...[more]

PMID: 36945547

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Project description:Borrelia spirochetes, causative agents of Lyme disease and relapsing fever (RF), have uniquely complex genomes, consisting of a linear chromosome and both circular and linear plasmids. The plasmids harbor genes important for the vector-host life cycle of these tick-borne bacteria. The role of plasmids from Lyme disease causing spirochetes is more refined compared to RF Borrelia because of limited plasmid-resolved genome assemblies for the latter. We recently addressed this limitation and found that three linear plasmid families (F6, F27, and F28) were syntenic across all the RF Borrelia species that we examined. Given this conservation, we further investigated the three plasmid families. The F6 family, also known as the megaplasmid, contained regions of repetitive DNA. The F27 was the smallest, encoding genes with unknown function. The F28 family encoded the putative expression locus for antigenic variation in all species except Borrelia hermsii and Borrelia anserina. Taken together, this work provides a foundation for future investigations to identify essential plasmid-localized genes that drive the vector-host life cycle of RF Borrelia. IMPORTANCE Borrelia spp. spirochetes are arthropod-borne bacteria found globally that infect humans and other vertebrates. RF borreliae are understudied and misdiagnosed pathogens because of the vague clinical presentation of disease and the elusive feeding behavior of argasid ticks. Consequently, genomics resources for RF spirochetes have been limited. Analyses of Borrelia plasmids have been challenging because they are often highly fragmented and unassembled in most available genome assemblies. By utilizing Oxford Nanopore Technologies, we recently generated plasmid-resolved genome assemblies for seven Borrelia spp. found in the Western Hemisphere. This current study is an in-depth investigation into the linear plasmids that were conserved and syntenic across species. We identified differences in genome structure and, importantly, in antigenic variation systems between species. This work is an important step in identifying crucial plasmid-localized genetic elements essential for the life cycle of RF spirochetes.

Project description:BackgroundTick-borne relapsing fever (TBRF) is a globally prevalent, yet under-studied vector-borne disease transmitted by soft and hard bodied ticks. While soft TBRF (sTBRF) spirochetes have been described for over a century, our understanding of the molecular mechanisms facilitating vector and host adaptation is poorly understood. This is due to the complexity of their small (~ 1.5 Mb) but fragmented genomes that typically consist of a linear chromosome and both linear and circular plasmids. A majority of sTBRF spirochete genomes' plasmid sequences are either missing or are deposited as unassembled sequences. Consequently, our goal was to generate complete, plasmid-resolved genomes for a comparative analysis of sTBRF species of the Western Hemisphere.ResultsUtilizing a Borrelia specific pipeline, genomes of sTBRF spirochetes from the Western Hemisphere were sequenced and assembled using a combination of short- and long-read sequencing technologies. Included in the analysis were the two recently isolated species from Central and South America, Borrelia puertoricensis n. sp. and Borrelia venezuelensis, respectively. Plasmid analyses identified diverse sequences that clustered plasmids into 30 families; however, only three families were conserved and syntenic across all species. We also compared two species, B. venezuelensis and Borrelia turicatae, which were isolated ~ 6,800 km apart and from different tick vector species but were previously reported to be genetically similar.ConclusionsTo truly understand the biological differences observed between species of TBRF spirochetes, complete chromosome and plasmid sequences are needed. This comparative genomic analysis highlights high chromosomal synteny across the species yet diverse plasmid composition. This was particularly true for B. turicatae and B. venezuelensis, which had high average nucleotide identity yet extensive plasmid diversity. These findings are foundational for future endeavors to evaluate the role of plasmids in vector and host adaptation.

Project description:BackgroundRelapsing fever (RF) borreliae are arthropod-borne spirochetes and some of them cause human diseases, which are characterized by relapsing or recurring episodes of fever. Recently, it has been classified into two groups: soft tick-borne RF (STRF) borreliae and hard tick-borne RF (HTRF) borreliae. STRF borreliae include classical RF agents and HTRF borreliae, the latter of which include B. miyamotoi, a human pathogen recently identified in Eurasia and North America.ResultsIn this study, we determined the genome sequences of 16 HTRF borreliae strains: 15 B. miyamotoi strains (9 from Hokkaido Island, Japan, 3 from Honshu Island, Japan, and 3 from Mongolia) and a Borrelia sp. tHM16w. Chromosomal gene synteny was highly conserved among the HTRF strains sequenced in this study, even though they were isolated from different geographic regions and different tick species. Phylogenetic analysis based on core gene sequences revealed that HTRF and STRF borreliae are clearly distinguishable, with each forming a monophyletic group in the RF borreliae lineage. Moreover, the evolutionary relationships of RF borreliae are consistent with the biological and ecological features of each RF borreliae sublineage and can explain the unique characteristics of Borrelia anserina. In addition, the pairwise genetic distances between HTRF borreliae strains were well correlated with those of vector species rather than with the geographical distances between strain isolation sites. This result suggests that the genetic diversification of HTRF borreliae is attributed to the speciation of vector ticks and that this relationship might be required for efficient transmission of HTRF borreliae within vector ticks.ConclusionsThe results of the present study, together with those from previous investigations, support the hypothesis that the common ancestor of borreliae was transmitted by hard-bodied ticks and that only STRF borreliae switched to using soft-bodied ticks as a vector, which was followed by the emergence of Borrelia recurrentis, lice-borne RF borreliae. Our study clarifies the phylogenetic relationships between RF borreliae, and the data obtained will contribute to a better understanding of the evolutionary history of RF borreliae.

Project description:Borrelia miyamotoi is a relapsing fever spirochete that shares the same vector as Lyme disease causing Borrelia. This epidemiological study of B. miyamotoi was conducted in rodent reservoirs, tick vectors and human populations simultaneously. A total of 640 rodents and 43 ticks were collected from Phop Phra district, Tak province, Thailand. The prevalence rate for all Borrelia species was 2.3% and for B. miyamotoi was 1.1% in the rodent population, while the prevalence rate was quite high in ticks collected from rodents with an infection rate of 14.5% (95% CI: 6.3-27.6%). Borrelia miyamotoi was detected in Ixodes granulatus collected from Mus caroli and Berylmys bowersi, and was also detected in several rodent species (Bandicota indica, Mus spp., and Leopoldamys sabanus) that live in a cultivated land, increasing the risk of human exposure. Phylogenetic analysis revealed that the B. miyamotoi isolates detected in rodents and I. granulatus ticks in this study were similar to isolates detected in European countries. Further investigation was conducted to determine the serological reactivity to B. miyamotoi in human samples received from Phop Phra hospital, Tak province and in rodents captured from Phop Phra district using an in-house, direct enzyme-linked immunosorbent assay (ELISA) assay with B. miyamotoi recombinant glycerophosphodiester-phosphodiesterase (rGlpQ) protein as coated antigen. The results showed that 17.9% (15/84) of human patients and 9.0% (41/456) of captured rodents had serological reactivity to B. miyamotoi rGlpQ protein in the study area. While a low level of IgG antibody titers (100-200) was observed in the majority of seroreactive samples, higher titers (400-1,600) were also detected in both humans and rodents. This study provides the first evidence of B. miyamotoi exposure in human and rodent populations in Thailand and the possible roles of local rodent species and Ixodes granulatus tick in its enzootic transmission cycle in nature.

Dataset Information

Comparative genomics analysis of three conserved plasmid families in the Western Hemisphere soft tick-borne relapsing fever borreliae provides insight into variation in genome structure and antigenic variation systems.

Importance

Publications

Comparative genomics analysis of three conserved plasmid families in the Western Hemisphere soft tick-borne relapsing fever borreliae provides insight into variation in genome structure and antigenic variation systems.

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