Evaluation of in vivo expressed Borrelia burgdorferi antigens for improved IgM serodiagnosis of early Lyme disease

2019 ◽  
Vol 93 (3) ◽  
pp. 196-202 ◽  
Author(s):  
Kevin S. Brandt ◽  
Amy J. Ullmann ◽  
Claudia R. Molins ◽  
Kalanthe Horiuchi ◽  
Brad J. Biggerstaff ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi

scholarly journals Fibroblast Protection of Borrelia burgdorferi from Doxycycline, Cefuroxime and Daptomycin Combination is Eliminated by Oregano or Carvacrol Essential Oil

2019 ◽  
Author(s):  
Chunxiang Bai ◽  
Hua Yang ◽  
Peng Cui ◽  
Rong Quan ◽  
Ying Zhang
Keyword(s):  
Lyme Disease ◽  
Essential Oil ◽  
Borrelia Burgdorferi ◽  
Drug Combination ◽  
Defense Mechanisms ◽  
Ex Vivo ◽  
Fibroblast Cells ◽  
Murine Fibroblast ◽  
Drug Regimens

AbstractBorrelia burgdorferi could be occasionally recovered from patients after antibiotic treatment, which indicates it may resist eradication by antibiotic and host defense mechanisms. Skin fibroblast cells have previously been shown to protect the killing of B. burgdorferi by ceftriaxone, a powerful antibiotic commonly used to treat Lyme disease. In this study, we evaluated if fibroblast cells could also protect against the doxycycline+ cefuroxime+ daptomycin drug combination which has previously been shown to completely eradicate highly persistent biofilm-like microcolonies of B. burgdorferi. To do so, we utilized a GFP-labeled B. burgdorferi for infection of murine fibroblast cells and assessed the effect of the drug combination on killing the bacteria in the presence or absence of the fibroblast cells. Surprisingly, we found that fibroblasts could protect B. burgdorferi from being completely killed by the drug combination doxycycline, cefuroxime and daptomycin, which eradicated B. burgdorferi completely in the absence of fibroblast cells. Interestingly, addition of essential oil carvacrol or oregano at 0.1% could enhance the activity of the doxycycline+ cefuroxime+ daptomycin drug combination and led to complete eradication of B. burgdorferi even in the presence of fibroblast cells. Further studies are needed to determine if the essential oil drug combinations could eradicate persistent B. burgdorferi infection in vivo in animal models. Our study provides a useful and convenient ex vivo model for evaluating different drug regimens needed for developing more effective treatment of persistent Lyme disease in the future.

scholarly journals Role of the BBA64 Locus of Borrelia burgdorferi in Early Stages of Infectivity in a Murine Model of Lyme Disease

2007 ◽  
Vol 76 (1) ◽  
pp. 391-402 ◽  
Author(s):  
Mahulena Maruskova ◽  
M. Dolores Esteve-Gassent ◽  
Valerie L. Sexton ◽  
J. Seshu
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Immunoblot Analysis ◽  
Open Reading Frames ◽  
Mammalian Host ◽  
Environmental Signals ◽  
Significant Difference ◽  
Linear Plasmid 54

ABSTRACT Borrelia burgdorferi, the causative agent of Lyme disease, undergoes rapid adaptive gene expression in response to environmental signals encountered during different stages of its life cycle in the arthropod vector or the mammalian host. Among all the plasmid-encoded genes of B. burgdorferi, several linear plasmid 54 (lp54)-encoded open reading frames (ORFs) exhibit the greatest differential expression in response to mammalian host-specific temperature, pH, and other uncharacterized signals. These ORFs include members of the paralogous gene family 54 (pgf 54), such as BBA64, BBA65, and BBA66, present on lp54. In an attempt to correlate transcriptional up-regulation of these pgf 54 members to their role in infectivity, we inactivated BBA64 and characterized the phenotype of this mutant both in vitro and in vivo. There were no major differences in the protein profiles between the BBA64 mutant and the control strains, while immunoblot analysis indicated that inactivation of BBA64 resulted in increased levels of BBA65. Moreover, there was no significant difference in the ability of the BBA64 mutant to infect C3H/HeN mice compared to that of its parental or complemented control strains as determined by culturing of viable spirochetes from infected tissues. However, enumeration of spirochetes using quantitative real-time PCR revealed tissue-specific differences, suggesting a minimal role for BBA64 in the survival of B. burgdorferi in select tissues. Infectivity analysis of the BBA64 mutant suggests that B. burgdorferi may utilize multiple determinants to establish infection in mammalian hosts.

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

2011 ◽  
Vol 18 (6) ◽  
pp. 901-906 ◽  
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.

scholarly journals Active and Passive Immunity against Borrelia burgdorferi Decorin Binding Protein A (DbpA) Protects against Infection

1998 ◽  
Vol 66 (5) ◽  
pp. 2143-2153 ◽  
Author(s):  
Mark S. Hanson ◽  
David R. Cassatt ◽  
Betty P. Guo ◽  
Nita K. Patel ◽  
Michael P. McCarthy ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Low Dose ◽  
Early Stage ◽  
Protein A ◽  
Sensu Stricto ◽  
Passive Immunity ◽  
In Vitro Growth

ABSTRACT Borrelia burgdorferi, the spirochete that causes Lyme disease, binds decorin, a collagen-associated extracellular matrix proteoglycan found in the skin (the site of entry for the spirochete) and in many other tissues. Two borrelial adhesins that recognize this proteoglycan, decorin binding proteins A and B (DbpA and DbpB, respectively), have recently been identified. Infection of mice by low-dose B. burgdorferi challenge elicited antibodies against DbpA and DbpB that were sustained at high levels, suggesting that these antigens are expressed in vivo. Scanning immunoelectron microscopy showed that DbpA was surface accessible on intact borreliae. Passive administration of DbpA antiserum protected mice from infection following challenge with heterologous B. burgdorferi sensu stricto isolates, even when serum administration was delayed for up to 4 days after challenge. DbpA is the first antigen target identified that is capable of mediating immune resolution of early, localizedB. burgdorferi infections. DbpA immunization also protected mice from B. burgdorferi challenge; DbpB immunization was much less effective. DbpA antiserum inhibited in vitro growth of manyB. burgdorferi sensu lato isolates of diverse geographic, phylogenetic, and clinical origins. In combination, these findings support a role for DbpA in the immunoprophylaxis of Lyme disease and suggest that DbpA vaccines have the potential to eliminate early-stageB. burgdorferi infections.

scholarly journals Repurposing Disulfiram (Tetraethylthiuram Disulfide) as a Potential Drug Candidate against Borrelia burgdorferi In Vitro and In Vivo

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 633 ◽  
Author(s):  
Hari-Hara S. K. Potula ◽  
Jahanbanoo Shahryari ◽  
Mohammed Inayathullah ◽  
Andrey Victorovich Malkovskiy ◽  
Kwang-Min Kim ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Post Infection ◽  
Systemic Disease ◽  
Organ Damage ◽  
Sensu Stricto ◽  
Effector Memory ◽  
Drug Candidate

Lyme disease caused by the Borrelia burgdorferi (Bb or B. burgdorferi) is the most common vector-borne, multi-systemic disease in the USA. Although most Lyme disease patients can be cured with a course of the first line of antibiotic treatment, some patients are intolerant to currently available antibiotics, necessitating the development of more effective therapeutics. We previously found several drugs, including disulfiram, that exhibited effective activity against B. burgdorferi. In the current study, we evaluated the potential of repurposing the FDA-approved drug, disulfiram for its borreliacidal activity. Our results indicate disulfiram has excellent borreliacidal activity against both the log and stationary phase B. burgdorferi sensu stricto B31 MI. Treatment of mice with disulfiram eliminated the B. burgdorferi sensu stricto B31 MI completely from the hearts and urinary bladder by day 28 post infection. Moreover, disulfiram-treated mice showed reduced expressions of inflammatory markers, and thus they were protected from histopathology and cardiac organ damage. Furthermore, disulfiram-treated mice showed significantly lower amounts of total antibody titers (IgM and IgG) at day 21 and total IgG2b at day 28 post infection. FACS analysis of lymph nodes revealed a decrease in the percentage of CD19+ B cells and an increase in total percentage of CD3+ T cells, CD3+ CD4+ T helpers, and naive and effector memory cells in disulfiram-treated mice. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic for treating Lyme disease.

scholarly journals Tick Saliva Reduces Adherence and Area of Human Neutrophils

2004 ◽  
Vol 72 (5) ◽  
pp. 2989-2994 ◽  
Author(s):  
Ruth R. Montgomery ◽  
Denise Lusitani ◽  
Anne de Boisfleury Chevance ◽  
Stephen E. Malawista
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Polymorphonuclear Leukocyte ◽  
Natural Infection ◽  
Ixodid Ticks ◽  
Human Neutrophils ◽  
Tick Saliva ◽  
Anti Inflammatory ◽  
Β2 Integrins

ABSTRACT During natural infection with the agent of Lyme disease, Borrelia burgdorferi, spirochetes are delivered with vector saliva, which contains anti-inflammatory and antihemostatic activities. We show here that the saliva of ixodid ticks reduces polymorphonuclear leukocyte (PMN) adhesion via downregulation of β2-integrins and decreases the efficiency of PMN in the uptake and killing of spirochetes. Inhibition of integrin adhesion and signaling reduces anti-inflammatory functions of PMN. These effects may favor the initial survival of spirochetes in vivo.

scholarly journals Characterization of Unique Regions of Borrelia burgdorferi Surface-Located Membrane Protein 1

2010 ◽  
Vol 78 (11) ◽  
pp. 4477-4487 ◽  
Author(s):  
Xiuli Yang ◽  
Tiffany R. Lenhart ◽  
Toru Kariu ◽  
Juan Anguita ◽  
Darrin R. Akins ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Membrane Protein ◽  
Borrelia Burgdorferi ◽  
Surface Protein ◽  
Integral Membrane Protein ◽  
Terminal Region ◽  
Pathogen Persistence ◽  
Bactericidal Effects ◽  
Organ Specific

ABSTRACT The pathogen of Lyme disease, Borrelia burgdorferi, produces a putative surface protein termed “surface-located membrane protein 1” (Lmp1). Lmp1 has been shown previously to assist the microbe in evasion of host-acquired immune defenses and in the establishment of persistent infection of mammals. Here, we show that Lmp1 is an integral membrane protein with surface-exposed N-terminal, middle, and C-terminal regions. During murine infection, antibodies recognizing these three protein regions were produced. Separate immunization of mice with each of the discrete regions exerted differential effects on spirochete survival during infection. Notably, antibodies against the C-terminal region primarily interfered with B. burgdorferi persistence in the joints, while antibodies specific to the N-terminal region predominantly affected pathogen levels in the heart, including the development of carditis. Genetic reconstitution of lmp1 deletion mutants with the lmp1 N-terminal region significantly enhanced its ability to resist the bactericidal effects of immune sera and also was observed to increase pathogen survival in vivo. Taken together, the combined data suggest that the N-terminal region of Lmp1 plays a distinct role in spirochete survival and other parts of the protein are related to specific functions corresponding to pathogen persistence and tropism during infection that is displayed in an organ-specific manner. The findings reported here underscore the fact that surface-exposed regions of Lmp1 could potentially serve as vaccine targets or antigenic regions that could alter the course of natural Lyme disease.

scholarly journals Vaccination against Lyme disease caused by diverse Borrelia burgdorferi.

1995 ◽  
Vol 181 (1) ◽  
pp. 215-221 ◽  
Author(s):  
E Fikrig ◽  
S R Telford ◽  
R Wallich ◽  
M Chen ◽  
Y Lobet ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Classification Systems ◽  
Surface Proteins ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Natural Mode ◽  
Naturally Occurring ◽  
Vector Borne

Diversity and mutations in the genes for outer surface proteins (Osps) A and B of Borrelia burgdorferi sensu lato (B. burgdorferi), the spirochetal agent of Lyme disease, suggests that a monovalent OspA or OspB vaccine may not provide protection against antigenically variable naturally occurring B. burgdorferi. We now show that OspA or OspB immunizations protect mice from tick-borne infection with heterogeneous B. burgdorferi from different geographic regions. This result is in distinct contrast to in vitro killing analyses and in vivo protection studies using syringe injections of B. burgdorferi as the challenge inoculum. Evaluations of vaccine efficacy against Lyme disease and other vector-borne infections should use the natural mode of transmission and not be predicated on classification systems or assays that do not rely upon the vector to transmit infection.

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