scholarly journals Interaction between Borrelia miyamotoi variable major proteins Vlp15/16 and Vlp18 with plasminogen and complement

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Frederik L. Schmidt ◽  
Valerie Sürth ◽  
Tim K. Berg ◽  
Yi-Pin Lin ◽  
Joppe W. Hovius ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Physiological Activity ◽  
Factor H ◽  
Ixodid Ticks ◽  
Borrelia Miyamotoi ◽  
Relapsing Fever ◽  
Interacting Protein ◽  
Protein Protein Interaction ◽  
Distinct Variable ◽  
Variable Major Proteins

AbstractBorrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and Vlp18 all of which are currently being evaluated as antigens for the serodiagnosis of BMD. Comparative analyses identified Vlp15/16 but not Vsp1 and Vlp18 as a plasminogen-interacting protein of B. miyamotoi. Furthermore, Vlp15/16 bound plasminogen in a dose-dependent fashion with high affinity. Binding of plasminogen to Vlp15/16 was significantly inhibited by the lysine analog tranexamic acid suggesting that the protein–protein interaction is mediated by lysine residues. By contrast, ionic strength did not have an effect on binding of plasminogen to Vlp15/16. Of relevance, plasminogen bound to the borrelial protein cleaved the chromogenic substrate S-2251 upon conversion by urokinase-type plasminogen activator (uPa), demonstrating it retained its physiological activity. Interestingly, further analyses revealed a complement inhibitory activity of Vlp15/16 and Vlp18 on the alternative pathway by a Factor H-independent mechanism. More importantly, both borrelial proteins protect serum sensitive Borrelia garinii cells from complement-mediated lysis suggesting multiple roles of these two variable major proteins in immune evasion of B. miyamotoi.

scholarly journals Whole genome sequencing of Borrelia miyamotoi isolate Izh-4: reference for a complex bacterial genome

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Konstantin V. Kuleshov ◽  
Gabriele Margos ◽  
Volker Fingerle ◽  
Joris Koetsveld ◽  
Irina A. Goptar ◽  
...  
Keyword(s):  
Single Molecule ◽  
Bacterial Genome ◽  
Borrelia Miyamotoi ◽  
Whole Genome ◽  
Relapsing Fever ◽  
Linear Chromosome ◽  
The North ◽  
Long Read ◽  
Variable Major Proteins ◽  
Tick Vectors

Abstract Background The genus Borrelia comprises spirochaetal bacteria maintained in natural transmission cycles by tick vectors and vertebrate reservoir hosts. The main groups are represented by a species complex including the causative agents of Lyme borreliosis and relapsing fever group Borrelia. Borrelia miyamotoi belongs to the relapsing fever group of spirochetes and forms distinct populations in North America, Asia, and Europe. As all Borrelia species B. miyamotoi possess an unusual and complex genome consisting of a linear chromosome and a number of linear and circular plasmids. The species is considered an emerging human pathogen and an increasing number of human cases are being described in the Northern hemisphere. The aim of this study was to produce a high quality reference genome that will facilitate future studies into genetic differences between different populations and the genome plasticity of B. miyamotoi. Results We used multiple available sequencing methods, including Pacific Bioscience single-molecule real-time technology (SMRT) and Oxford Nanopore technology (ONT) supplemented with highly accurate Illumina sequences, to explore the suitability for whole genome assembly of the Russian B. miyamotoi isolate, Izh-4. Plasmids were typed according to their potential plasmid partitioning genes (PF32, 49, 50, 57/62). Comparing and combining results of both long-read (SMRT and ONT) and short-read methods (Illumina), we determined that the genome of the isolate Izh-4 consisted of one linear chromosome, 12 linear and two circular plasmids. Whilst the majority of plasmids had corresponding contigs in the Asian B. miyamotoi isolate FR64b, there were only four that matched plasmids of the North American isolate CT13–2396, indicating differences between B. miyamotoi populations. Several plasmids, e.g. lp41, lp29, lp23, and lp24, were found to carry variable major proteins. Amongst those were variable large proteins (Vlp) subtype Vlp-α, Vlp-γ, Vlp-δ and also Vlp-β. Phylogenetic analysis of common plasmids types showed the uniqueness in Russian/Asian isolates of B. miyamotoi compared to other isolates. Conclusions We here describe the genome of a Russian B. miyamotoi clinical isolate, providing a solid basis for future comparative genomics of B. miyamotoi isolates. This will be a great impetus for further basic, molecular and epidemiological research on this emerging tick-borne pathogen.

scholarly journals Whole genome sequencing of Borrelia miyamotoi isolate Izh-4: reference for a complex bacterial genome

2019 ◽  
Author(s):  
Konstantin V. Kuleshov ◽  
Gabriele Margos ◽  
Volker Fingerle ◽  
Joris Koetsveld ◽  
Irina A. Goptar ◽  
...  
Keyword(s):  
Single Molecule ◽  
Bacterial Genome ◽  
Borrelia Miyamotoi ◽  
Whole Genome ◽  
Relapsing Fever ◽  
Linear Chromosome ◽  
The North ◽  
Long Read ◽  
Variable Major Proteins ◽  
Tick Vectors

Abstract Background: The genus Borrelia comprises spirochaetal bacteria maintained in natural transmission cycles by tick vectors and vertebrate reservoir hosts. The main groups are represented by a species complex including the causative agents of Lyme borreliosis and relapsing fever group Borrelia. Borrelia miyamotoi belongs to the relapsing-fever group of spirochetes and forms distinct populations in North America, Asia, and Europe. As all Borrelia species B. miyamotoi possess an unusual and complex genome consisting of a linear chromosome and a number of linear and circular plasmids. The species is considered an emerging human pathogen and an increasing number of human cases are being described in the Northern hemisphere. The aim of this study was to produce a high quality reference genome that will facilitate future studies into genetic differences between different populations and the genome plasticity of B. miyamotoi. Results: We used multiple available sequencing methods, including Pacific Bioscience single-molecule real-time technology (SMRT) and Oxford Nanopore technology (ONT) supplemented with highly accurate Illumina sequences, to explore the suitability for whole genome assembly of the Russian B. miyamotoi isolate, Izh-4. Plasmids were typed according to their potential plasmid partitioning genes (PF32, 49, 50, 57/62). Comparing and combining results of both long-read (SMRT and ONT) and short-read methods (Illumina), we determined that the genome of the isolate Izh-4 consisted of one linear chromosome, 12 linear and two circular plasmids. Whilst the majority of plasmids had corresponding contigs in the Asian B. miyamotoi isolate FR64b, there were only four that matched plasmids of the North American isolate CT13-2396, indicating differences between B. miyamotoi populations. Several plasmids, e.g. lp41, lp29, lp23, and lp24, were found to carry variable major proteins. Amongst those were variable large proteins (Vlp) subtype Vlp-α, Vlp-γ, Vlp-δ and also Vlp-β. Phylogenetic analysis of common plasmids types showed the uniqueness in Russian/Asian isolates of B. miyamotoi compared to other isolates. Conclusions: We here describe the genome of a Russian B. miyamotoi clinical isolate, providing a solid basis for future comparative genomics of B. miyamotoi isolates. This will be a great impetus for further basic, molecular and epidemiological research on this emerging tick-borne pathogen.

scholarly journals Whole genome sequencing of Borrelia miyamotoi isolate Izh-4: reference for a complex bacterial genome

2019 ◽  
Author(s):  
Konstantin V. Kuleshov ◽  
Gabriele Margos ◽  
Volker Fingerle ◽  
Joris Koetsveld ◽  
Irina A. Goptar ◽  
...  
Keyword(s):  
Single Molecule ◽  
Bacterial Genome ◽  
Borrelia Miyamotoi ◽  
Whole Genome ◽  
Relapsing Fever ◽  
Linear Chromosome ◽  
The North ◽  
Long Read ◽  
Variable Major Proteins ◽  
Tick Vectors

Abstract Background The genus Borrelia comprises spirochaetal bacteria maintained in natural transmission cycles by tick vectors and vertebrate reservoir hosts. The main groups are represented by a species complex including the causative agents of Lyme borreliosis and relapsing fever group Borrelia . Borrelia miyamotoi belongs to the relapsing-fever group of spirochetes and forms distinct populations in North America, Asia, and Europe. As all Borrelia species B. miyamotoi possess an unusual and complex genome consisting of a linear chromosome and a number of linear and circular plasmids. The species is considered a relatively new human pathogen and an increasing number of human cases are being described in the Northern hemisphere. The aim of this study was to produce a high quality reference genome that will facilitate future studies into genetic differences between different populations and the genome plasticity of B. miyamotoi . Results We used multiple available sequencing methods, including Pacific Bioscience single-molecule real-time technology (SMRT) and Oxford Nanopore technology (ONT) supplemented with highly accurate Illumina sequences, to explore the suitability for whole genome assembly of the Russian B. miyamotoi isolate, Izh-4. Plasmids were typed according to their potential plasmid partitioning genes (PF32, 49, 50, 57/62). Comparing and combining results of both long-read methods (SMRT and ONT), we determined that the genome of the Izh-4 consisted of one linear chromosome, 12 linear and two circular plasmids. Whilst the majority of plasmids had corresponding assembly fragments in the Asian B. miyamotoi isolate FR64b, there were only four that matched plasmids of the North American isolate CT13-2396, indicating differences between B. miyamotoi populations. Several plasmids, e.g. lp41, lp29, lp23, and lp24, were found to carry variable major proteins. Amongst those were variable large proteins (Vlp) subtype Vlp-α, Vlp-γ, Vlp-δ and also Vlp-β. Phylogenetic analysis of common plasmids types showed the uniqueness in Russian/Asian isolates of B. miyamotoi compared to other isolates. Conclusions We here describe the genome of a Russian B. miyamotoi clinical isolate, providing a solid basis for future comparative genomics of B. miyamotoi isolates. This will be a great impetus for further basic, molecular and epidemiological research on this emerging tick-borne pathogen.

scholarly journals Spatial and temporal patterns of the emerging tick-borne pathogen Borrelia miyamotoi in blacklegged ticks (Ixodes scapularis) in New York

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
F. Keesing ◽  
D. J. McHenry ◽  
M. H. Hersh ◽  
R. S. Ostfeld
Keyword(s):  
New York ◽  
Ixodes Scapularis ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Infection ◽  
Ixodid Ticks ◽  
Transovarial Transmission ◽  
Infection Prevalence ◽  
Borrelia Miyamotoi ◽  
Spatial And Temporal Patterns ◽  
Reservoir Hosts

AbstractBorrelia miyamotoi, a bacterium that causes relapsing fever, is found in ixodid ticks throughout the northern hemisphere. The first cases of human infection with B. miyamotoi were identified in 2011. In the eastern USA, blacklegged ticks (Ixodes scapularis) become infected by feeding on an infected vertebrate host, or through transovarial transmission. We surveyed B. miyamotoi prevalence in ticks within forested habitats in Dutchess County, New York, and identified possible reservoir hosts. To assess spatial variation in infection, we collected questing nymphal ticks at > 150 sites. To assess temporal variation in infection, we collected questing nymphs for 8 years at a single study site. We collected questing larval ticks from nine plots to estimate the amount of transovarial transmission. To evaluate potential reservoir hosts, we captured 14 species of mammal and bird hosts naturally infested with larval blacklegged ticks and held these hosts in the laboratory until ticks fed to repletion and molted to nymphs. We determined infection for all ticks using quantitative polymerase chain reaction. The overall infection prevalence of questing nymphal ticks across all sites was ~ 1%, but prevalence at individual sites was as high as 9.1%. We detected no significant increase in infection through time. Only 0.4% of questing larval ticks were infected. Ticks having fed as larvae from short-tailed shrews, red squirrels, and opossums tended to have higher infection prevalence than did ticks having fed on other hosts. Further studies of the role of hosts in transmission are warranted. The locally high prevalence of B. miyamotoi in the New York/New England landscape suggests the importance of vigilance by health practitioners and the public.

scholarly journals New functional and structural insights from updated mutational databases for complement factor H, Factor I, membrane cofactor protein and C3

2014 ◽  
Vol 34 (5) ◽  
Author(s):  
Elizabeth Rodriguez ◽  
Pavithra M. Rallapalli ◽  
Amy J. Osborne ◽  
Stephen J. Perkins
Keyword(s):  
Alternative Pathway ◽  
Factor H ◽  
Complement Factor H ◽  
Complement C3 ◽  
Complement Factor ◽  
Membrane Cofactor Protein ◽  
Complement Alternative Pathway ◽  
Factor I ◽  
Mutational Hotspots ◽  
Structural Insights

A new compilation of 324 mutations in four major proteins from the complement alternative pathway reveals mutational hotspots in factor H and complement C3, and less so in factor I and membrane cofactor protein. Their associations with function are discussed.

scholarly journals Nizp1, a Novel Multitype Zinc Finger Protein That Interacts with the NSD1 Histone Lysine Methyltransferase through a Unique C2HR Motif

2004 ◽  
Vol 24 (12) ◽  
pp. 5184-5196 ◽  
Author(s):  
Anders Lade Nielsen ◽  
Poul Jørgensen ◽  
Thierry Lerouge ◽  
Margarita Cerviño ◽  
Pierre Chambon ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Sotos Syndrome ◽  
Dependent Manner ◽  
Interacting Protein ◽  
Protein Protein Interaction ◽  
Histone Lysine ◽  
Histone Lysine Methyltransferase ◽  
Lysine Methyltransferase

ABSTRACT Haploinsufficiency of the NSD1 gene is a hallmark of Sotos syndrome, and rearrangements of this gene by translocation can cause acute myeloid leukemia. The NSD1 gene product is a SET-domain histone lysine methyltransferase that has previously been shown to interact with nuclear receptors. We describe here a novel NSD1-interacting protein, Nizp1, that contains a SCAN box, a KRAB-A domain, and four consensus C2H2-type zinc fingers preceded by a unique finger derivative, referred to herein as the C2HR motif. The C2HR motif functions to mediate protein-protein interaction with the cysteine-rich (C5HCH) domain of NSD1 in a Zn(II)-dependent fashion, and when tethered to RNA polymerase II promoters, represses transcription in an NSD1-dependent manner. Mutations of the cysteine or histidine residues in the C2HR motif abolish the interaction of Nizp1 with NSD1 and compromise the ability of Nizp1 to repress transcription. Interestingly, converting the C2HR motif into a canonical C2H2 zinc finger has a similar effect. Thus, Nizp1 contains a novel type of zinc finger motif that functions as a docking site for NSD1 and is more than just a degenerate evolutionary remnant of a C2H2 motif.

scholarly journals Functional Mapping of YadA- and Ail-Mediated Binding of Human Factor H to Yersinia enterocolitica Serotype O:3

2008 ◽  
Vol 76 (11) ◽  
pp. 5016-5027 ◽  
Author(s):  
Marta Biedzka-Sarek ◽  
Saara Salmenlinna ◽  
Markus Gruber ◽  
Andrei N. Lupas ◽  
Seppo Meri ◽  
...  
Keyword(s):  
Yersinia Enterocolitica ◽  
Alternative Pathway ◽  
Outer Membrane Proteins ◽  
Factor H ◽  
Complement Alternative Pathway ◽  
Human Host ◽  
Serotype O ◽  
Complement Resistance ◽  
Sense And Respond ◽  
Active Complement

ABSTRACT Yersinia enterocolitica is an enteric pathogen that exploits diverse means to survive in the human host. Upon Y. enterocolitica entry into the human host, bacteria sense and respond to variety of signals, one of which is the temperature. Temperature in particular has a profound impact on Y. enterocolitica gene expression, as most of its virulence factors are expressed exclusively at 37°C. These include two outer membrane proteins, YadA and Ail, that function as adhesins and complement resistance (CR) factors. Both YadA and Ail bind the functionally active complement alternative pathway regulator factor H (FH). In this study, we characterized regions on both proteins involved in CR and the interaction with FH. Twenty-eight mutants having short (7 to 41 amino acids) internal deletions within the neck and stalk of YadA and two complement-sensitive site-directed Ail mutants were constructed to map the CR and FH binding regions of YadA and Ail. Functional analysis of the YadA mutants revealed that the stalk of YadA is required for both CR and FH binding and that FH appears to target several conformational and discontinuous sites of the YadA stalk. On the other hand, the complement-sensitive Ail mutants were not affected in FH binding. Our results also suggested that Ail- and YadA-mediated CR does not depend solely on FH binding.

scholarly journals Type VI secretion system sheaths as nanoparticles for antigen display

2016 ◽  
Vol 113 (11) ◽  
pp. 3042-3047 ◽  
Author(s):  
Elena Del Tordello ◽  
Olga Danilchanka ◽  
Andrew J. McCluskey ◽  
John J. Mekalanos
Keyword(s):  
Protein A ◽  
Secretion System ◽  
Factor H ◽  
Soluble Antigen ◽  
Tubular Structures ◽  
Type Vi Secretion System ◽  
Interacting Protein ◽  
Serum Bactericidal Assay ◽  
Heterologous Antigens ◽  
Bacterial Type

The bacterial type 6 secretion system (T6SS) is a dynamic apparatus that translocates proteins between cells by a mechanism analogous to phage tail contraction. T6SS sheaths are cytoplasmic tubular structures composed of stable VipA-VipB (named for ClpV-interacting protein A and B) heterodimers. Here, the structure of the VipA/B sheath was exploited to generate immunogenic multivalent particles for vaccine delivery. Sheaths composed of VipB and VipA fused to an antigen of interest were purified from Vibrio cholerae or Escherichia coli and used for immunization. Sheaths displaying heterologous antigens generated better immune responses against the antigen and different IgG subclasses compared with soluble antigen alone. Moreover, antigen-specific antibodies raised against sheaths presenting Neisseria meningitidis factor H binding protein (fHbp) antigen were functional in a serum bactericidal assay. Our results demonstrate that multivalent nanoparticles based on the T6SS sheath represent a versatile scaffold for vaccine applications.

scholarly journals De Novo Atypical Haemolytic Uremic Syndrome after Kidney Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Arnaud Devresse ◽  
Martine de Meyer ◽  
Selda Aydin ◽  
Karin Dahan ◽  
Nada Kanaan
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Alternative Pathway ◽  
Factor H ◽  
Complement Factor ◽  
Haemolytic Uremic Syndrome ◽  
Hinman Syndrome ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

De novo thrombotic microangiopathy (TMA) can occur after kidney transplantation. An abnormality of the alternative pathway of complement must be suspected and searched for, even in presence of a secondary cause. We report the case of a 23-year-old female patient who was transplanted with a kidney from her mother for end-stage renal disease secondary to Hinman syndrome. Early after transplantation, she presented with 2 episodes of severe pyelonephritis, associated with acute kidney dysfunction and biological and histological features of TMA. Investigations of the alternative pathway of the complement system revealed atypical haemolytic uremic syndrome secondary to complement factor I mutation, associated with mutations in CD46 and complement factor H related protein genes. Plasma exchanges followed by eculizumab injections allowed improvement of kidney function without, however, normalization of creatinine.

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