The Complement Binding and Inhibitory Protein CbiA of Borrelia miyamotoi Degrades Extracellular Matrix Components by Interacting with Plasmin(ogen)

Nguyen, Ngocthach; Röttgerding, Florian; Devraj, Gayatri; Lin, Yi‐Pin; Kraiczy, Peter

doi:10.3389/fcimb.2018.00023

Cited by 12 publications

(33 citation statements)

References 68 publications

(126 reference statements)

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“…Interestingly, B. miyamotoi and B. lonestari are transmitted by hard ticks, leading to the proposed distinction of hard tick-borne relapsing fever (HTBRF) or B. miyamotoi disease (BMD). 1 , 10 , 18 , 19 In the USA, B. miyamotoi strains have been detected in the hard ticks Ixodes scapularis and Ixodes pacificus , 6 , 9 , 20 , 21 while B. lonestari DNA has been detected in the hard tick Amblyomma americanum . 5 B. miyamotoi also varies genetically depending on geographic region, leading to the concept of the B. miyamotoi sensu lato complex.…”

Section: Discussionmentioning

confidence: 99%

Relapsing fever <em>Borrelia</em> in California: a pilot serological study

Middelveen¹,

Shah²,

Fesler³

et al. 2018

IJGM

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BackgroundBorrelia spirochetes are tick-borne Gram-negative bacteria that cause disease in humans and animals. Although many studies have focused on Borrelia burgdorferi (Bb), the agent of Lyme disease, recent studies have examined the role of Relapsing Fever Borrelia (RFB) in human disease. In this pilot study, we have evaluated serological reactivity against Bb and RFB in patients residing in California.MethodsSerological testing for reactivity to Bb and RFB antigens was performed in 543 patients with suspected tick-borne illness using a Western blot technique. Further evaluation of a subset of 321 patients residing in California was obtained. Serum samples were tested for IgM and IgG antibodies reactive with Bb and RFB, and samples were classified by county of residence according to Bb reactivity alone, RFB reactivity alone, and dual reactivity against Bb and RFB. Seroreactivity was ranked in counties with the highest absolute number and the highest prevalence of positive samples.ResultsOf the 543 total serum samples, 32% were positive for Bb, 22% were positive for RFB, and 7% were positive for both Bb and RFB. Of the 321 serum samples from patients residing in California, 33% were positive for Bb, 27% were positive for RFB, and 11% were positive for both Bb and RFB. In the California cohort, the highest rates of positive serological testing for Bb were found in Santa Clara, Alameda, and Contra Costa counties, while the highest rates of positive serological testing for RFB were found in Santa Clara, Alameda, Marin, and San Francisco counties. The highest rates of dual reactivity against Bb and RFB were found in Contra Costa, Alameda, and San Francisco counties. Among the 24 counties with patients who were tested, Bb seropositivity alone was found in four counties, RFB seropositivity alone was found in two counties, and seropositivity for both Bb and RFB was found in 14 counties.ConclusionResults of this pilot study suggest that seroreactivity against Bb and RFB is widespread in California, and dual exposure to Bb and RFB may complicate the diagnosis of tick-borne disease. Greater awareness of RFB and broader screening for this tick-borne infection is warranted.

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Section: Discussionmentioning

confidence: 99%

Relapsing fever <em>Borrelia</em> in California: a pilot serological study

Middelveen¹,

Shah²,

Fesler³

et al. 2018

IJGM

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“…In California, B. miyamotoi, B. hermsii, and B. parkeri human infections were reported [32], and B. coriaceae was detected in ticks, although human infection was not confirmed [32,39]. B. miyamotoi was originally detected in Japan in 1995, but it is thought to have recently arrived in the Western hemisphere [38,40]; in the USA, it was detected in the North American ixodid ticks I. scapularis and I. pacificus [35,38,41,42].…”

Section: Discussionmentioning

confidence: 99%

“…It is important to recognize that classification is a human concept and the organisms encompassing the genus Borrelia fall within a continuous spectrum of organisms rather than into well-defined genetically distinct groups that are easily categorized. Some species that genetically fall into the RFB group, such as B. miyamotoi and B. lonestari , are vectored by ixodid ticks rather than argasid ticks, and there is, therefore, a proposal to classify them into a new group—hard tick-borne relapsing fever (HTBRF) [ 4 , 13 , 38 , 42 , 44 ]. B. miyamotoi demonstrates genetic differences in accord with different geographic regions and different vectors, leading to the proposal to establish grouping into a B. miyamotoi sensu lato complex [ 14 , 35 , 45 , 46 , 47 , 48 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Lyme Disease: Diversity of Borrelia Species in California and Mexico Detected Using a Novel Immunoblot Assay

Fesler

Shah²,

Middelveen

et al. 2020

Healthcare

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Background: With more than 300,000 new cases reported each year in the United States of America (USA), Lyme disease is a major public health concern. Borrelia burgdorferi sensu stricto (Bbss) is considered the primary agent of Lyme disease in North America. However, multiple genetically diverse Borrelia species encompassing the Borrelia burgdorferi sensu lato (Bbsl) complex and the Relapsing Fever Borrelia (RFB) group are capable of causing tickborne disease. We report preliminary results of a serological survey of previously undetected species of Bbsl and RFB in California and Mexico using a novel immunoblot technique. Methods: Serum samples were tested for seroreactivity to specific species of Bbsl and RFB using an immunoblot method based on recombinant Borrelia membrane proteins, as previously described. A sample was recorded as seropositive if it showed immunoglobulin M (IgM) and/or IgG reactivity with at least two proteins from a specific Borrelia species. Results: The patient cohort consisted of 90 patients residing in California or Mexico who met the clinical case definition of chronic Lyme disease. Immunoblot testing revealed that 42 patients were seropositive for Bbsl (Group 1), while 56 patients were seropositive for RFB (Group 2). Eight patients were seropositive for both Bbsl and RFB species. Group 1 included patients who were seropositive for Bbss (14), B. californiensis (eight), B. spielmanii (10), B. afzelii/B. garinii (10), and mixed infections that included B. mayonii (three). Group 2 included patients who were seropositive for B. hermsii (nine), B. miyamotoi (seven), B. turicatae (nine), and B. turcica (two). In the remaining Group 1 and Group 2 patients, the exact Borrelia species could not be identified using the immunoblot technique. Conclusions: Lyme disease is associated with a diverse group of Borrelia species in California and Mexico. Current testing for Lyme disease focuses on detection of Bbss, possibly resulting in missed diagnoses and failure to administer appropriate antibiotic therapy in a timely manner. The genetic diversity of Borrelia spirochetes must be considered in future Lyme disease test development.

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“…Distinct complement-interacting proteins including BhCRASP-1, HcpA, and CbiA exhibit multiple binding specificities to host-derived fluid phase proteins such as plasminogen (33,34,36,44) (Figure 1A, Table 1). Plasminogen is known to bind to C3, C3b, C3d, and C5 and upon activation to plasmin, C3 and C5 degradation takes place (49).…”

Section: Inactivation Of Complement By Acquisition Of Plasminogenmentioning

confidence: 99%

“…Plasminogen is also able to enhance Factor I-mediated C3b degradation in the presence of FH (49). Previous studies demonstrated that plasmin(ogen) bound to B. hermsii HS1, B. recurrentis A1, and B. parkeri decreases the amount of C3b molecules deposited on the borrelial surface (33,34,36) or lead to degradation of C3b when purified HcpA, BpcA, and CbiA, respectively, have been employed (34,36,44). Thus, degradation of C3 and C5 appears an additional strategy of RFB to successful overcome host immune defenses.…”

Section: Inactivation Of Complement By Acquisition Of Plasminogenmentioning

confidence: 99%

Immune Evasion Strategies of Relapsing Fever Spirochetes

Röttgerding

Kraiczy

2020

Front. Immunol.

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Relapsing fever (RF) is claimed a neglected arthropod-borne disease caused by a number of diverse human pathogenic Borrelia (B.) species. These RF borreliae are separated into the groups of tick-transmitted species including B. duttonii, B. hermsii, B. parkeri, B. turicatae, B. hispanica, B. persica, B. caucasica, and B. myiamotoi, and the louse-borne Borrelia species B. recurrentis. As typical blood-borne pathogens achieving high cell concentrations in human blood, RF borreliae (RFB) must outwit innate immunity, in particular complement as the first line of defense. One prominent strategy developed by RFB to evade innate immunity involves inactivation of complement by recruiting distinct complement regulatory proteins, e.g., C1 esterase inhibitor (C1-INH), C4b-binding protein (C4BP), factor H (FH), FH-like protein-1 (FHL-1), and factor H-related proteins FHR-1 and FHR-2, or binding of individual complement components and plasminogen, respectively. A number of multi-functional, complement and plasminogen-binding molecules from distinct Borrelia species have previously been identified and characterized, exhibiting considerable heterogeneity in their sequences, structures, gene localization, and their capacity to bind host-derived proteins. In addition, RFB possess a unique system of antigenic variation, allowing them to change the composition of surface-exposed variable major proteins, thus evading the acquired immune response of the human host. This review focuses on the current knowledge of the immune evasion strategies by RFB and highlights the role of complement-interfering and infection-associated molecules for the pathogenesis of RFB.

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The Complement Binding and Inhibitory Protein CbiA of Borrelia miyamotoi Degrades Extracellular Matrix Components by Interacting with Plasmin(ogen)

Cited by 12 publications

References 68 publications

Relapsing fever <em>Borrelia</em> in California: a pilot serological study

Relapsing fever <em>Borrelia</em> in California: a pilot serological study

Lyme Disease: Diversity of Borrelia Species in California and Mexico Detected Using a Novel Immunoblot Assay

Immune Evasion Strategies of Relapsing Fever Spirochetes

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