Anti-Borrelia burgdorferi Antibody Profile in Post-Lyme Disease Syndrome

ABSTRACTPatients with post-Lyme disease syndrome (PLDS) report persistent symptoms of pain, fatigue, and/or concentration and memory disturbances despite antibiotic treatment for Lyme borreliosis. The etiopathogenesis of these symptoms remains unknown and no effective therapies have been identified. We sought to examine the antiborrelia antibody profile in affected patients with the aim of finding clues to the mechanism of the syndrome and its relationship to the original spirochetal infection. Serum specimens from 54 borrelia-seropositive PLDS patients were examined for antibodies toBorrelia burgdorferiproteins p18, p25, p28, p30, p31, p34, p39, p41, p45, p58, p66, p93, and VlsE by automated immunoblotting and software-assisted band analysis. The presence of serum antibodies to the 31-kDa band was further investigated by examination of reactivity against purified recombinant OspA protein. Control specimens included sera from 14 borrelia-seropositive individuals with a history of early localized or disseminated Lyme disease who were symptom free (post-Lyme healthy group), as well as 20 healthy individuals without serologic evidence or history of Lyme disease. In comparison to the post-Lyme healthy group, higher frequencies of antibodies to p28 (P< 0.05), p30 (P< 0.05), p31 (P< 0.0001), and p34 (P< 0.05) proteins were found in the PLDS group. Assessment of antibody reactivity to recombinant OspA confirmed the presence of elevated levels in PLDS patients (P< 0.005). The described antiborrelia antibody profile in PLDS offers clues about the course of the antecedent infection in affected patients, which may be useful for understanding the pathogenic mechanism of the disease.

Download Full-text

Evaluation of Disulfiram Drug Combinations and Identification of Other More Effective Combinations against Stationary Phase Borrelia burgdorferi

Antibiotics ◽

10.3390/antibiotics9090542 ◽

2020 ◽

Vol 9 (9) ◽

pp. 542 ◽

Cited By ~ 1

Author(s):

Hector Alvarez-Manzo ◽

Yumin Zhang ◽

Wanliang Shi ◽

Ying Zhang

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Stationary Phase ◽

Drug Exposure ◽

Drug Combinations ◽

Persistent Symptoms ◽

Exposure Experiment ◽

Vector Borne ◽

Treatment Alternatives ◽

Possible Cause

Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in USA, and 10–20% of patients will develop persistent symptoms despite treatment (“post-treatment Lyme disease syndrome”). B. burgdorferi persisters, which are not killed by the current antibiotics for Lyme disease, are considered one possible cause. Disulfiram has shown to be active against B. burgdorferi, but its activity against persistent forms is not well characterized. We assessed disulfiram as single drug and in combinations against stationary-phase B. burgdorferi culture enriched with persisters. Disulfiram was not very effective in the drug exposure experiment (survival rate (SR) 46.3%) or in combinations. Clarithromycin (SR 41.1%) and nitroxoline (SR 37.5%) were equally effective when compared to the current Lyme antibiotic cefuroxime (SR 36.8%) and more active than disulfiram. Cefuroxime + clarithromycin (SR 25.9%) and cefuroxime + nitroxoline (SR 27.5%) were significantly more active than cefuroxime + disulfiram (SR 41.7%). When replacing disulfiram with clarithromycin or nitroxoline in three-drug combinations, bacterial viability decreased significantly and subculture studies showed that combinations with these two drugs (cefuroxime + clarithromycin/nitroxoline + furazolidone/nitazoxanide) inhibited the regrowth, while disulfiram combinations did not (cefuroxime + disulfiram + furazolidone/nitazoxanide). Thus, clarithromycin and nitroxoline should be further assessed to determine their role as potential treatment alternatives in the future.

Download Full-text

Evaluation of RevA, a Fibronectin-Binding Protein of Borrelia burgdorferi, as a Potential Vaccine Candidate for Lyme Disease

Clinical and Vaccine Immunology ◽

10.1128/cvi.00758-12 ◽

2013 ◽

Vol 20 (6) ◽

pp. 892-899 ◽

Cited By ~ 12

Author(s):

Angela M. Floden ◽

Tammy Gonzalez ◽

Robert A. Gaultney ◽

Catherine A. Brissette

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Passive Immunization ◽

Surface Protein ◽

Surface Expression ◽

Content Type ◽

Good Target ◽

Potential Vaccine ◽

Mammalian Infection

ABSTRACTPrevious studies indicated that the Lyme disease spirocheteBorrelia burgdorferiexpresses the RevA outer surface protein during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA appears to be a good target for preventive therapies. RevA proteins are highly conserved across all Lyme borreliae, and antibodies against RevA protein are cross-reactive among RevA proteins from diverse strains. Mice infected withB. burgdorferimounted a rapid IgM response to RevA, followed by a strong IgG response that generally remained elevated for more than 12 months, suggesting continued exposure of RevA protein to the immune system. RevA antibodies were bactericidalin vitro. To evaluate the RevA antigen as a potential vaccine, mice were vaccinated with recombinant RevA and challenged withB. burgdorferiby inoculation with a needle or by a tick bite. Cultured tissues from all treatment groups were positive forB. burgdorferi. Vaccinated animals also appeared to have similar levels ofB. burgdorferiDNA compared to nonvaccinated controls. Despite its antigenicity, surface expression, and the production of bactericidal antibodies against it, RevA does not protect againstBorrelia burgdorferiinfection in a mouse model. However, passive immunization with anti-RevA antibodies did prevent infection, suggesting the possible utility of RevA-based immunotherapeutics or vaccine.

Download Full-text

Altered Murine Tissue Colonization by Borrelia burgdorferi following Targeted Deletion of Linear Plasmid 17-Carried Genes

Infection and Immunity ◽

10.1128/iai.05984-11 ◽

2012 ◽

Vol 80 (5) ◽

pp. 1773-1782 ◽

Cited By ~ 9

Author(s):

Timothy Casselli ◽

Yvonne Tourand ◽

Troy Bankhead

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Mutant Strain ◽

Genetic Manipulation ◽

Infectious Clone ◽

Linear Plasmid ◽

Peripheral Tissues ◽

Content Type ◽

Immunodeficient Mice

ABSTRACTThe causative agent of Lyme disease,Borrelia burgdorferi, possesses a segmented genome comprised of a single linear chromosome and upwards of 23 linear and circular plasmids. Much of what is known about plasmid-borne genes comes from studying laboratory clones that have spontaneously lost one or more plasmids duringin vitropassage. Some plasmids, including the linear plasmid lp17, are never or rarely reported to be lost during routine culture; therefore, little is known about the requirement of these conserved plasmids for infectivity. In this study, the effects of deleting regions of lp17 were examined bothin vitroandin vivo. A mutant strain lacking the genesbbd16tobbd25showed no deficiency in the ability to establish infection or disseminate to the bloodstream of mice; however, colonization of peripheral tissues was delayed. Despite the ability to colonize ear, heart, and joint tissues, this mutant exhibited a defect in bladder tissue colonization for up to 56 days postinfection. This phenotype was not observed in immunodeficient mice, suggesting that bladder colonization by the mutant strain was inhibited by an adaptive immune-based mechanism. Moreover, the mutant displayed increased expression of outer surface protein Cin vitro, which was correlated with the absence of the genebbd18. To our knowledge, this is the first report involving genetic manipulation of lp17 in an infectious clone ofB. burgdorferiand reveals for the first time the effects of lp17 gene deletion during murine infection by the Lyme disease spirochete.

Download Full-text

Outer Surface Protein C Peptide Derived from Borrelia burgdorferi Sensu Stricto as a Target for Serodiagnosis of Early Lyme Disease

Clinical and Vaccine Immunology ◽

10.1128/cvi.00608-12 ◽

2013 ◽

Vol 20 (4) ◽

pp. 474-481 ◽

Cited By ~ 27

Author(s):

Paul M. Arnaboldi ◽

Rudra Seedarnee ◽

Mariya Sambir ◽

Steven M. Callister ◽

Josephine A. Imparato ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Bacterial Species ◽

Erythema Migrans ◽

Early Infection ◽

Enzyme Linked Immunosorbent Assay ◽

Attractive Alternative ◽

Serum Samples ◽

Peptide Epitope ◽

Content Type

ABSTRACTCurrent serodiagnostic assays for Lyme disease are inadequate at detecting early infection due to poor sensitivity and nonspecificity that arise from the use of whole bacteria or bacterial proteins as assay targets; both targets contain epitopes that are cross-reactive with epitopes found in antigens of other bacterial species. Tests utilizing peptides that contain individual epitopes highly specific forBorrelia burgdorferias diagnostic targets are an attractive alternative to current assays. Using an overlapping peptide library, we mapped linear epitopes in OspC, a critical virulence factor ofB. burgdorferirequired for mammalian infection, and confirmed the results by enzyme-linked immunosorbent assay (ELISA). We identified a highly conserved 20-amino-acid peptide epitope, OspC1. Via ELISA, OspC1 detected specific IgM and/or IgG in 60 of 98 serum samples (62.1%) obtained from patients with erythema migrans (early Lyme disease) at the time of their initial presentation. By comparison, the commercially available OspC peptide PepC10 detected antibody in only 48 of 98 serum samples (49.0%). In addition, OspC1 generated fewer false-positive results among negative healthy and diseased (rheumatoid arthritis and positive Rapid Plasma Reagin [RPR+] test result) control populations than did PepC10. Both highly specific and more sensitive than currently available OspC peptides, OspC1 could have value as a component of a multipeptide Lyme disease serological assay with significantly improved capabilities for the diagnosis of early infection.

Download Full-text

Antibodies to Borrelia burgdorferi OspA, OspC, OspF, and C6 Antigens as Markers for Early and Late Infection in Dogs

Clinical and Vaccine Immunology ◽

10.1128/cvi.05653-11 ◽

2012 ◽

Vol 19 (4) ◽

pp. 527-535 ◽

Cited By ~ 32

Author(s):

Bettina Wagner ◽

Heather Freer ◽

Alicia Rollins ◽

David Garcia-Tapia ◽

Hollis N. Erb ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

The United States ◽

Sensu Stricto ◽

Antibody Responses ◽

Surface Proteins ◽

Early Infection ◽

Enzyme Linked Immunosorbent Assay ◽

Content Type ◽

Antibody Levels

ABSTRACTLyme disease in the United States is caused byBorrelia burgdorferisensu stricto, which is transmitted to mammals by infected ticks.Borreliaspirochetes differentially express immunogenic outer surface proteins (Osp). Our aim was to evaluate antibody responses to Osp antigens to aid the diagnosis of early infection and the management of Lyme disease. We analyzed antibody responses during the first 3 months after the experimental infection of dogs using a novel multiplex assay. Results were compared to those obtained with two commercial assays detecting C6 antigen. Multiplex analysis identified antibodies to OspC and C6 as early as 3 weeks postinfection (p.i.) and those to OspF by 5 weeks p.i. Antibodies to C6 and OspF increased throughout the study, while antibodies to OspC peaked between 7 and 11 weeks p.i. and declined thereafter. A short-term antibody response to OspA was observed in 3/8 experimentally infected dogs on day 21 p.i. Quant C6 enzyme-linked immunosorbent assay (ELISA) results matched multiplex results during the first 7 weeks p.i.; however, antibody levels subsequently declined by up to 29%. Immune responses then were analyzed in sera from 125 client-owned dogs and revealed high agreement between antibodies to OspF and C6 as robust markers for infection. Results from canine patient sera supported that OspC is an early infection marker and antibodies to OspC decline over time. The onset and decline of antibody responses toB. burgdorferiOsp antigens and C6 reflect their differential expression during infection. They provide valuable tools to determine the stage of infection, treatment outcomes, and vaccination status in dogs.

Download Full-text

Disulfide-Mediated Oligomer Formation in Borrelia burgdorferi Outer Surface Protein C, a Critical Virulence Factor and Potential Lyme Disease Vaccine Candidate

Clinical and Vaccine Immunology ◽

10.1128/cvi.05004-11 ◽

2011 ◽

Vol 18 (6) ◽

pp. 901-906 ◽

Cited By ~ 10

Author(s):

Christopher G. Earnhart ◽

DeLacy V. L. Rhodes ◽

Richard T. Marconi

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Disulfide Bonds ◽

Vaccine Candidate ◽

Site Directed Mutagenesis ◽

Yield Strain ◽

Content Type ◽

Oligomer Formation ◽

Lyme Disease Vaccine

ABSTRACTBorrelia burgdorferiOspC is an outer membrane lipoprotein required for the establishment of infection in mammals. Due to its universal distribution amongB. burgdorferisensu lato strains and high antigenicity, it is being explored for the development of a next-generation Lyme disease vaccine. An understanding of the surface presentation of OspC will facilitate efforts to maximize its potential as a vaccine candidate. OspC forms homodimers at the cell surface, and it has been hypothesized that it may also form oligomeric arrays. Here, we employ site-directed mutagenesis to test the hypothesis that interdimeric disulfide bonds at cysteine 130 (C130) mediate oligomerization.B. burgdorferiB31ospCwas replaced with a C130A substitution mutant to yield strain B31::ospC(C130A). Recombinant protein was also generated. Disulfide-bond-dependent oligomer formation was demonstrated and determined to be dependent on C130. Oligomerization was not required forin vivofunction, as B31::ospC(C130A) retained infectivity and disseminated normally. The total IgG response and the induced isotype pattern were similar between mice infected with untransformed B31 and those infected with the B31::ospC(C130A) strain. These data indicate that the immune response to OspC is not significantly altered by formation of OspC oligomers, a finding that has significant implications in Lyme disease vaccine design.

Download Full-text

The Borrelia burgdorferi Glycosaminoglycan Binding Protein Bgp in the B31 Strain Is Not Essential for Infectivity despite Facilitating Adherence and Tissue Colonization

Infection and Immunity ◽

10.1128/iai.00667-17 ◽

2017 ◽

Vol 86 (2) ◽

Cited By ~ 5

Author(s):

Samantha Schlachter ◽

Janakiram Seshu ◽

Tao Lin ◽

Steven Norris ◽

Nikhat Parveen

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Binding Protein ◽

Mammalian Host ◽

Infection Model ◽

Binding Assays ◽

Content Type ◽

Mouse Infection Model ◽

Successful Infection

ABSTRACTThe Lyme disease-causing organismBorrelia burgdorferiis transmitted into the mammalian host by an infected-tick bite. Successful infection relies on the ability of this extracellular pathogen to persist and colonize different tissues.B. burgdorferiencodes a large number of adhesins that are able to interact with host ligands to facilitate adherence and tissue colonization. Multiple glycosaminoglycan binding proteins present inB. burgdorferioffer a degree of redundancy of function during infection, and this highlights the importance of glycosaminoglycans as host cell receptors for spirochete adherence. Of particular interest in this study isBorreliaglycosaminoglycan binding protein (Bgp), which binds to heparin-related glycosaminoglycans. The properties of abgptransposon mutant and atrans-complemented derivative were compared to those of the wild-typeB. burgdorferiin thein vitrobinding assays and in infection studies using a C3H/HeJ mouse infection model. We determined that the loss of Bgp impairs spirochete adherence, infectivity, and tissue colonization, resulting in a reduction of inflammatory manifestations of Lyme disease. Although Bgp is not essential for infectivity, it is an important virulence factor ofB. burgdorferithat allows adherence and tissue colonization and contributes to disease severity.

Download Full-text

Lyme disease, An Emerging Infection in Nepal: A Case Report

Journal of Universal College of Medical Sciences ◽

10.3126/jucms.v8i02.34309 ◽

2020 ◽

Vol 8 (02) ◽

pp. 90-92

Author(s):

Prabin Khatri ◽

Chandra Mohan Sah ◽

Rano Mal Piryani ◽

Shatdal Chaudhary ◽

Puspa Raj Dhakal ◽

...

Keyword(s):

Differential Diagnosis ◽

Case Report ◽

Lyme Disease ◽

Borrelia Burgdorferi ◽

Joint Pain ◽

Histological Findings ◽

Multisystemic Disease ◽

Tingling Sensation ◽

History Of ◽

The Given

ABSTRACT Lyme disease, an infectious multisystemic disease is caused by "Borrelia burgdorferi". It is a spirochete transmitted by the Ixodes tick. Until today, only one case has been reported from Nepal. Here we report case of a 50-year female from Gulmi, who presented with a history of fever, multiple joint pain, tiredness, tingling sensation, and a painful brownish raised lesion over the neck and anterior chest. The clinical diagnosis was confirmed by histological findings typical of erythema chronicum migrans and by serology. The patient was treated successfully with doxycycline. This is the second case report of Lyme disease from Nepal and the first documented case who presented with typical erythema chronicum migrans. We suspect that Lyme disease might not have been considered in the differential diagnosis of fever with rash and joint pain in Nepal and suggest that it is to be kept as a differential in the given scenario.

Download Full-text

AWARENESS OF LYME BORRELIOSIS OF THE PATIENTS OF TERNOPIL REGIONAL TB DISPENSARY

International Journal of Medicine and Medical Research ◽

10.11603/ijmmr.2413-6077.2017.1.7810 ◽

2017 ◽

Author(s):

L. P. Melnyk ◽

L. A. Hryshchuk ◽

M. Koziol–Montewka ◽

P. S. Tabas ◽

R. O. Klos

Keyword(s):

Nervous System ◽

Lyme Disease ◽

Borrelia Burgdorferi ◽

Lyme Borreliosis ◽

Preventive Measures ◽

Epidemiological Data ◽

Sufficient Information ◽

Tick Bites ◽

The World ◽

History Of

Background. Lyme disease has many clinical features similar tothose in sarcoidosis and tuberculosis. Epidemiological data in the world, in particular in Ukraine, proves the increase in Lyme borreliosis incidence. Ternopil region is endemic with Lyme borreliosis.Objective. The research was aimed to investigate the prevalence of infection with Borrelia burgdorferi and epidemiology features of borreliosis among the patients of Ternopil Regional TB Dispensary.Methods. In total, 29 patients were admitted to Departments of Differential Diagnostic, TB Therapy and TB Surgery of Ternopil Regional TB Dispensary in October 2016-January 2017. All the surveyed answered the questions of an integrated international questionnaire, where they noted the area and a number of tick bites, described the removal method, noted the survey for borreliosis pathogen and complaints after tick bites.Results. It was established that 5 respondents had a history of tick bites episodes, but only in one case the patient was examined of borreliosis. Tick bites were noticed in 3 patients with sarcoidosis and 1 with tuberculosis (TB) and exudative pleurisy, respectively.Conclusions. The absence of appeals for medical care, lack of sufficient information on Lyme borreliosis and disuse of preventive measures for tick bites by the interviewed patients of Ternopil regional TB dispensary departments proves the need of improvement of health education on Lyme borreliosis (LB) among this category of population. 24 (82.7%) of 29 respondents did not remember the tick bite. The symptoms of (LB) are similar to those in sarcoidosis and tuberculosis (pleural lesions, heart, joints, nervous system, skin), and the presence of tick bites gives the reasons to examine these patients of Borrelia burgdorferi senso lato.

Download Full-text