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PloS One 2019In a recent publication in PLOS ONE, Gabriele Margos and colleagues have questioned the division of the genus Borrelia into two genera on the basis that the differences...
Distinction between Borrelia and Borreliella is more robustly supported by molecular and phenotypic characteristics than all other neighbouring prokaryotic genera: Response to Margos' et al. "The genus Borrelia reloaded" (PLoS ONE 13(12): e0208432).
In a recent publication in PLOS ONE, Gabriele Margos and colleagues have questioned the division of the genus Borrelia into two genera on the basis that the differences in percentage of conserved proteins (POCP) between these two groups is >50%, which an earlier study has suggested as the threshold for differentiating prokaryotic genera. However, the POCP threshold is a poorly characterized and rarely used criterion for establishing distinction among prokaryotic genera. Detailed evaluation of the intergeneric POCP values for 37 genera from 3 different families (viz. Enterobacteriaceae- 24 genera, Morganellaceae-8 genera and Cystobacteraceae-5 genera) presented here shows that the POCP values for all genera within each of these families exceeded >58%. Thus, the suggested POCP threshold is not a useful criterion for delimitation of genus boundary and the objection by Margos et al. on this ground is invalid. Additionally, Margos et al. have questioned the specificities of ~15-20% of the conserved signature indels (CSIs) described in our work. However, as shown here, this concern is due to misunderstanding of the results and the CSIs in question are still highly-specific characteristics of the members of these genera and they provide important information regarding the evolutionary relationships of two new reptiles-echidna-related species viz. Borrelia turcica and Candidatus Borrelia tachyglossi to other Borrelia species. Results presented here show that both these species are deeper-branching members of the genus Borrelia and their placement within this genus is strongly supported by phylogenetic analyses and multiple uniquely shared CSIs with the other Borrelia species. Based on the large body of evidence derived from phylogenetic, genomic, molecular, phenotypic and clinical features, it is contended that the characteristics clearly distinguishing the Borrelia and Borreliella genera are far more numerous and of different kinds than those discerning most (all) other neighbouring genera of prokaryotes. Thus, the placement of these two groups of microorganisms into distinct genera, Borrelia and Borreliella, which clearly recognizes the differences among them, is highly appropriate and it should lead to a better understanding of the clinical, molecular and biological differences between these two important groups of microbes.
Topics: Bacterial Proteins; Borrelia; DNA, Bacterial; Phylogeny; RNA, Ribosomal, 16S
PubMed: 31454394
DOI: 10.1371/journal.pone.0221397 -
International Journal of Biological... 2016Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal...
Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria.
Topics: Anti-Infective Agents; Biofilms; Borrelia; Borrelia burgdorferi; Borrelia burgdorferi Group; Doxycycline; Microbial Sensitivity Tests; Micronutrients; Phytochemicals; Spirochaetales
PubMed: 27570483
DOI: 10.7150/ijbs.16060 -
Parasites & Vectors Jul 2021Borrelia miyamotoi is a newly described relapsing fever spirochete transmitted by ixodid tick species. Little is known about the prevalence of B. miyamotoi infections in...
BACKGROUND
Borrelia miyamotoi is a newly described relapsing fever spirochete transmitted by ixodid tick species. Little is known about the prevalence of B. miyamotoi infections in humans and ticks in Inner Mongolia, China. Therefore, we investigated the prevalence of B. miyamotoi in Ixodes persulcatus ticks, and we aimed to isolateB. miyamotoi from I. persulcatus from four regions of Greater Khingan, Inner Mongolia, China.
METHODS
From May to June each year during the period 2016-2019, host-seeking adult I. persulcatus ticks were collected from vegetation. Genomic DNA was prepared from half of each tick body for PCR template, and the remaining half was used to cultivate B. miyamotoi in BSK-M medium. We employed quantitative real-time PCR (qPCR) to detect Borrelia DNA in the ticks and to calculate the prevalence of B. miyamotoi and infections with other borreliae. For characterization of the isolated B. miyamotoi, we performed draft genome sequencing and multilocus sequencing analysis (MLSA).
RESULTS
A total of 2656 adult I. persulcatus ticks were collected. The overall prevalence of relapsing fever (RF) borreliae in ticks was 5.0% (134/2656) and that of Lyme disease (LD) borreliae was 43.8% (1164/2656). Co-infection with RF and LD borreliae was observed in 63 ticks (2.4%). Ticks that were positive for RF borreliae by qPCR were subjected to glycerophosphodiester diester phosphodiesterase gene (glpQ) PCR amplification and sequencing, through which we identified the RF borrelia specimens as B. miyamotoi. Furthermore, the B. miyamotoi strain Hetao-1 was isolated from I. persulcatus, and a draft genome sequence was obtained from the isolate. Sequencing determined the strain Hetao-1 genome to be approximately 906.1 kbp in length (28.9% average GC content), and MLSA identified the strain as ST633, which has previously been reported in Japan and Mongolia.
CONCLUSION
We detected B. miyamotoi from I. persulcatus ticks collected in Inner Mongolia, and successfully isolated a B. miyamotoi strain. To our knowledge, this is the first study to culture a B. miyamotoi isolate from China. The data on the prevalence of B. miyamotoi and other borreliae in I. persulcatus ticks will be fundamental for future epidemiological studies of B. miyamotoi disease in Inner Mongolia.
Topics: Animals; Bacterial Typing Techniques; Borrelia; China; Epidemiological Monitoring; Genomics; Humans; Ixodes; Multilocus Sequence Typing; Real-Time Polymerase Chain Reaction; Relapsing Fever
PubMed: 34274015
DOI: 10.1186/s13071-021-04809-z -
Parasites & Vectors Feb 2021The incidence of Lyme borreliosis varies over time and space through as yet incompletely understood mechanisms. In Europe, Lyme borreliosis is caused by infection with a...
BACKGROUND
The incidence of Lyme borreliosis varies over time and space through as yet incompletely understood mechanisms. In Europe, Lyme borreliosis is caused by infection with a Borrelia burgdorferi (s.l.) genospecies, which is primarily transmitted by a bite of Ixodes ricinus nymphs. The aim of this study was to investigate the spatial and temporal variation in nymphal infection prevalence of B. burgdorferi (s.l.) (NIP), density of questing nymphs (DON) and the resulting density of infected nymphs (DIN).
METHODS
We investigated the infection rates in I. ricinus nymphs that were collected monthly between 2009 and 2016 in 12 locations in the Netherlands. Using generalized linear mixed models, we explored how the NIP, DON and DIN varied during the seasons, between years and between locations. We also determined the genospecies of the Borrelia infections and investigated whether the genospecies composition differed between locations.
RESULTS
The overall NIP was 14.7%. A seasonal pattern in infection prevalence was observed, with higher estimated prevalences in the summer than in the spring and autumn. This, combined with higher nymphal densities in summer, resulted in a pronounced summer peak in the estimated DIN. Over the 7.5-year study period, a significant decrease in infection prevalence was found, as well as a significant increase in nymphal density. These two effects appear to cancel each other out; the density of infected nymphs, which is the product of NIP × DON, showed no significant trend over years. Mean infection prevalence (NIP, averaged over all years and all months) varied considerably between locations, ranging from 5 to 26%. Borrelia genospecies composition differed between locations: in some locations almost all infections consisted of B. afzelii, whereas other locations had more diverse genospecies compositions.
CONCLUSION
In the Netherlands, the summer peak in DIN is a result of peaks in both NIP and DON. No significant trend in DIN was observed over the years of the study, and variations in DIN between locations were mostly a result of the variation in DON. There were considerable differences in acarological risk between areas in terms of infection prevalence and densities of ticks as well as in Borrelia genospecies composition.
Topics: Animals; Borrelia; Borrelia burgdorferi; Ixodes; Netherlands; Nymph; Seasons
PubMed: 33627166
DOI: 10.1186/s13071-021-04607-7 -
Ticks and Tick-borne Diseases Jan 2023Four genospecies from the Borrelia burgdorferi sensu lato complex were detected in Ixodes persulcatus and Ixodes pavlovskyi ticks from Siberia and genetically...
Detection and genetic characterization of a putative novel Borrelia genospecies in Ixodes apronophorus / Ixodes persulcatus / Ixodes trianguliceps sympatric areas in Western Siberia.
Four genospecies from the Borrelia burgdorferi sensu lato complex were detected in Ixodes persulcatus and Ixodes pavlovskyi ticks from Siberia and genetically characterized. The presence of Borrelia spp. in Ixodes apronophorus and Ixodes trianguliceps ticks found in Asia has never been studied. In this study, genetic diversity of B. burgdorferi s.l. was investigated in three I. persulcatus / I. trianguliceps / I. apronophorus sympatric habitats in Western Siberia. Three groups of samples were examined: (i) ticks that were taken from rodents and molted in a laboratory; (ii) non-molted ticks collected from rodents; (iii) specimens from small mammals. Expectedly, Borrelia afzelii and Borrelia bavariensis were detected in I. persulcatus and in small mammals from the studied locations. Borrelia bavariensis was first found in molted I. apronophorus and I. trianguliceps. Identical genovariants of B. bavariensis were found in I. apronophorus, I. trianguliceps, and I. persulcatus. In addition, a new Borrelia genovariant was discovered in non-molted and molted I. apronophorus and non-molted I. persulcatus and I. trianguliceps, as well as in small mammals. This new genovariant was genetically characterized using MLST and single locus sequence analysis, which indicated that the new Borrelia genovariant significantly differs from all known Borrelia species. We propose the name "Candidatus Borrelia sibirica" for this putative new species.
Topics: Animals; Borrelia; Ixodes; Multilocus Sequence Typing; Asia; Mammals
PubMed: 36335681
DOI: 10.1016/j.ttbdis.2022.102075 -
BMC Genomics May 2022Tick-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)...
BACKGROUND
Tick-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.
RESULTS
Utilizing 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.
CONCLUSIONS
To 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.
Topics: Borrelia; Genomics; Humans; Plasmids; Relapsing Fever; Sequence Analysis, DNA
PubMed: 35641918
DOI: 10.1186/s12864-022-08523-7 -
Molecular Microbiology Apr 2019Lyme borreliosis is caused by multiple species of the spirochete bacteria Borrelia burgdorferi sensu lato. The spirochetes are transmitted by ticks to vertebrate hosts,... (Review)
Review
Lyme borreliosis is caused by multiple species of the spirochete bacteria Borrelia burgdorferi sensu lato. The spirochetes are transmitted by ticks to vertebrate hosts, including small- and medium-sized mammals, birds, reptiles, and humans. Strain-to-strain variation in host-specific infectivity has been documented, but the molecular basis that drives this differentiation is still unclear. Spirochetes possess the ability to evade host immune responses and colonize host tissues to establish infection in vertebrate hosts. In turn, hosts have developed distinct levels of immune responses when invaded by different species/strains of Lyme borreliae. Similarly, the ability of Lyme borreliae to colonize host tissues varies among different spirochete species/strains. One potential mechanism that drives this strain-to-strain variation of immune evasion and colonization is the polymorphic outer surface proteins produced by Lyme borreliae. In this review, we summarize research on strain-to-strain variation in host competence and discuss the evidence that supports the role of spirochete-produced protein polymorphisms in driving this variation in host specialization. Such information will provide greater insights into the adaptive mechanisms driving host and Lyme borreliae association, which will lead to the development of interventions to block pathogen spread and eventually reduce Lyme borreliosis health burden.
Topics: Adaptive Immunity; Animals; Bacterial Outer Membrane Proteins; Borrelia burgdorferi; Host Microbial Interactions; Host Specificity; Humans; Immunity, Innate; Lyme Disease; Mice; Polymorphism, Genetic
PubMed: 30666741
DOI: 10.1111/mmi.14209 -
Frontiers in Cellular and Infection... 2020Spirochetes of the genus are divided into relapsing fever borreliae and Lyme disease borreliae. Immunoserological assays have been poorly developed for relapsing fever... (Review)
Review
Spirochetes of the genus are divided into relapsing fever borreliae and Lyme disease borreliae. Immunoserological assays have been poorly developed for relapsing fever borreliae, where direct detection methods are more adapted to the pathophysiology of these infections presenting with massive bacteraemia. However, emergence of the novel agent of relapsing fever has renewed interest in serology in this context. In Lyme disease, because direct detection methods show low sensitivity, serology plays a central role in the diagnostic strategy. This diagnostic strategy is based on a two-tier methodology involving a first test (ELISA) with high sensitivity and acceptable specificity and a second, more specific test (western blot) for diagnostic confirmation. The most frequent limitations and pitfalls of serology are cross reactions, false IgM positivity, a seronegative window period at the early time of the infection, and serologic scars with a suspicion of reinfection. International guidelines have thus been proposed to avoid these difficulties with interpretation. Finally, unconventional diagnostic tests have been developed recently in the context of a highly publicized disease, with widely varying results, some of which have no available evidence-based data. New two-tier testing strategies using two ELISA tests (C6 and WCS for example) to replace immunoblot are currently proposed by some authors and guidelines, and promising new tests such as CXCL-13 in CSF are promising tools for the improvement of the diagnosis of Lyme borreliosis.
Topics: Antibodies, Bacterial; Borrelia; Borrelia burgdorferi Group; Enzyme-Linked Immunosorbent Assay; Humans; Lyme Disease; Relapsing Fever
PubMed: 32509603
DOI: 10.3389/fcimb.2020.00241 -
Research in Microbiology 1992Antigenic variation and strain heterogeneity have been demonstrated for the pathogenic Borrelia species, i.e. B. burgdorferi and the relapsing fever borreliae. In... (Review)
Review
Antigenic variation and strain heterogeneity have been demonstrated for the pathogenic Borrelia species, i.e. B. burgdorferi and the relapsing fever borreliae. In relapsing fever, new borrelia serotypes emerge at a high rate spontaneously, a mechanism that is caused by DNA rearrangements on linear plasmid translocating genes coding for variable major proteins from previous silent to expression sites (i.e. from inner sites to telomeric sites of the plasmid). As a result of this variation, the borreliae escape the immune response of the host, thus leading to the relapse phenomenon. In B. burgdorferi, which is the causative agent of the multisystem disorder Lyme borreliosis, there is also a growing body of findings that antigenic variation is involved in pathogenesis of the disease. Phenotypic variation of strains in vitro concerns the size and the amount of surface-associated proteins (OspA, OspB and pC). There are indications that OspA and OspB truncations are due to deletions within the ospAB operon caused by recombination events, and that OspA/OspB-less mutants lack the 49-kb plasmid that bears the ospAB operon. With the increasing number of isolates obtained from various geographic and biological sources, it became apparent that B. burgdorferi is immunologically and genetically more heterogeneous, as previously believed. The major outer surface proteins OspA and OspB (which have been efficient antigens in vaccine studies) are heterogeneous at a genetic level. The same degree of genetic non-identity was observed for the pC protein. Other proteins like flagellin and the highly specific immunodominant p100 range protein show a lower degree of non-identity. Recombinant OspA, pC, p100 range protein and flagellin have been hyperexpressed in E. coli and these proteins are immunologically reactive. This allows further research for development of vaccines and diagnostic tools. B. burgdorferi isolates have been investigated with genotyping (DNA hybridization, PCR and 16S rRNA analysis) as well as serotyping by various authors. Comparison of the different methods has shown good agreement when the same strains have been investigated. No correlation could be found between different phenotypic and genotypic groups with respect to the ability to cause arthritis in SCID mice. A serotyping system based on immunological differences in OspA detected by a panel of monoclonal antibodies has been proposed. Serotyping a large number of B. burgdorferi isolates has shown a striking predominance of the OspA serotype 2 among European isolates from human skin, in contrast to isolates from ticks or CSF.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Antigenic Variation; Bacterial Outer Membrane Proteins; Borrelia burgdorferi Group; Flagellin; In Vitro Techniques; Recombination, Genetic; Serotyping
PubMed: 1475519
DOI: 10.1016/0923-2508(92)90116-6 -
International Journal of Infectious... Dec 2013To determine the genetic identity of Borrelia spirochetes isolated from patients with an unusual skin lesion of prurigo pigmentosa (PP) in Taiwan. The causative agents...
Molecular detection and genetic identification of Borrelia garinii and Borrelia afzelii from patients presenting with a rare skin manifestation of prurigo pigmentosa in Taiwan.
OBJECTIVES
To determine the genetic identity of Borrelia spirochetes isolated from patients with an unusual skin lesion of prurigo pigmentosa (PP) in Taiwan. The causative agents responsible for human borreliosis were clarified.
METHODS
Serum samples and skin specimens were collected from 14 patients with suspected PP and five controls. Serological testing by Western immunoblot analysis and isolation of Borrelia spirochetes from skin specimens were used to verify the Borrelia infection. Genetic identities of isolated spirochetes were determined by analyzing the gene sequences amplified by PCR assay based on the 5S (rrf)-23S (rrl) intergenic spacer amplicon gene of Borrelia burgdorferi sensu lato.
RESULTS
Borrelia spirochetes were isolated from skin biopsies of three patients. Serological evidence of Borrelia infection in these patients was also confirmed by elevated IgG and IgM antibodies against the major protein antigens of B. burgdorferi. Phylogenetic analysis revealed that these detected spirochetes are genetically affiliated to the genospecies of Borrelia garinii and Borrelia afzelii with high sequence homology within the genospecies of B. garinii (91.0-98.7%) and B. afzelii (97%).
CONCLUSIONS
This study provides the first evidence of B. garinii and B. afzelii isolated and identified in patients with PP. Whether this unusual skin lesion is a new manifestation of Lyme disease needs to be studied further.
Topics: Adult; Borrelia; Borrelia Infections; DNA, Ribosomal Spacer; Female; Humans; Male; Middle Aged; Molecular Sequence Data; Phylogeny; Prurigo; Serotyping; Skin; Taiwan
PubMed: 24103333
DOI: 10.1016/j.ijid.2013.08.004