Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease.

Lyme disease (LD) results from the most prevalent tick-borne infection in North America, with over 476,000 estimated cases annually. The disease is caused by which transmits through the bite of Ixodid ticks. Most cases treated soon after infection are resolved by a short course of oral antibiotics.

Migration Assays for Evaluation of Chemoattractants in Tick Saliva.

Uptake of the Lyme disease spirochete by its tick vector requires not only chemical signals present in the tick's saliva but a responsive phenotype by the living in the mammalian host. This is the principle behind xenodiagnosis, wherein pathogen is detected by vector acquisition. To study migration of toward tick saliva, with the goal of identifying chemoattractant molecules, we tested multiple assays and compared migration of host-adapted spirochetes to those cultured in vitro.

Multi-platform Approach for Microbial Biomarker Identification Using as a Model.

The identification of microbial biomarkers is critical for the diagnosis of a disease early during infection. However, the identification of reliable biomarkers is often hampered by a low concentration of microbes or biomarkers within host fluids or tissues. We have outlined a multi-platform strategy to assess microbial biomarkers that can be consistently detected in host samples, using , the causative agent of Lyme disease, as an example.

Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding.

The efficacy and accepted regimen of antibiotic treatment for Lyme disease has been a point of significant contention among physicians and patients. While experimental studies in animals have offered evidence of post-treatment persistence of Borrelia burgdorferi, variations in methodology, detection methods and limitations of the models have led to some uncertainty with respect to translation of these results to human infection. With all stages of clinical Lyme disease having previously been described in nonhuman primates, this animal model was selected in order to most closely mimic human infection and response to treatment.

Antagonist of the neurokinin-1 receptor curbs neuroinflammation in ex vivo and in vitro models of Lyme neuroborreliosis.

Background: Lyme neuroborreliosis (LNB) can affect both the peripheral (PNS) and the central nervous systems (CNS); it is caused by the spirochete Borrelia burgdorferi. The neuropeptide substance P (SP) is an important mediator of both neuroinflammation and blood-brain barrier dysfunction, through its NK1 receptor. Increased levels of SP have been shown to correlate with cell death.

Phosphoenolpyruvate Phosphotransferase System Components Modulate Gene Transcription and Virulence of Borrelia burgdorferi.

The phosphoenolpyruvate phosphotransferase system (PEP-PTS) and adenylate cyclase (AC) IV (encoded by BB0723 [cyaB]) are well conserved in different species of Borrelia. However, the functional roles of PEP-PTS and AC in the infectious cycle of Borrelia have not been characterized previously. We examined 12 PEP-PTS transporter component mutants by needle inoculation of mice to assess their ability to cause mouse infection.

Inflammation in the pathogenesis of lyme neuroborreliosis.

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated.

Correction: Persistence of in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection.

[This corrects the article on p. e29914 in vol. 7.

Feeding of ticks on animals for transmission and xenodiagnosis in Lyme disease research.

Transmission of the etiologic agent of Lyme disease, Borrelia burgdorferi, occurs by the attachment and blood feeding of Ixodes species ticks on mammalian hosts. In nature, this zoonotic bacterial pathogen may use a variety of reservoir hosts, but the white-footed mouse (Peromyscus leucopus) is the primary reservoir for larval and nymphal ticks in North America. Humans are incidental hosts most frequently infected with B.

Analysis of an ordered, comprehensive STM mutant library in infectious Borrelia burgdorferi: insights into the genes required for mouse infectivity.

The identification of genes important in the pathogenesis of Lyme disease Borrelia has been hampered by exceedingly low transformation rates in low-passage, infectious organisms. Using the infectious, moderately transformable B. burgdorferi derivative 5A18NP1 and signature-tagged versions of the Himar1 transposon vector pGKT, we have constructed a defined transposon library for the efficient genome-wide investigation of genes required for wild-type pathogenesis, in vitro growth, physiology, morphology, and plasmid replication.

Dynamic longitudinal antibody responses during Borrelia burgdorferi infection and antibiotic treatment of rhesus macaques.

Infection with Borrelia burgdorferi elicits robust yet disparate antibody responses in infected individuals. A longitudinal assessment of antibody responses to multiple diagnostic antigens following experimental infection and treatment has not previously been reported. Our goal was to identify a combination of antigens that could indicate infection at all phases of disease and response to antibiotic treatment.

Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection.

The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic efficacy using nonhuman primates. Rhesus macaques were infected with B.

Central role of the Holliday junction helicase RuvAB in vlsE recombination and infectivity of Borrelia burgdorferi.

Antigenic variation plays a vital role in the pathogenesis of many infectious bacteria and protozoa including Borrelia burgdorferi, the causative agent of Lyme disease. VlsE, a 35 kDa surface-exposed lipoprotein, undergoes antigenic variation during B. burgdorferi infection of mammalian hosts, and is believed to be a critical mechanism by which the spirochetes evade immune clearance.

Possible role of glial cells in the onset and progression of Lyme neuroborreliosis.

Background: Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis.

Antigenicity and recombination of VlsE, the antigenic variation protein of Borrelia burgdorferi, in rabbits, a host putatively resistant to long-term infection with this spirochete.

Borrelia burgdorferi, the Lyme disease pathogen, employs several immune-evasive strategies to survive in mammals. Unlike mice, major reservoir hosts for B. burgdorferi, rabbits are considered to be nonpermissive hosts for persistent infection.

Dominant epitopes of the C6 diagnostic peptide of Borrelia burgdorferi are largely inaccessible to antibody on the parent VlsE molecule.

Lyme borreliosis (LB) is a disease for which antibody-based detection assays are often required for diagnosis. The variable surface molecule VlsE and IR6, one of its invariable regions, are commonly targeted by the antibody response in infected individuals. A series of enzyme-linked immunosorbent assays was performed to comparatively examine the antibody responses of North American LB patients (n = 37) to VlsE and invariable segments of this molecule.

Infectivity of the highly transformable BBE02- lp56- mutant of Borrelia burgdorferi, the Lyme disease spirochete, via ticks.

Infectious Borrelia burgdorferi strains that have increased transformability with the shuttle vector pBSV2 were recently constructed by inactivating the gene encoding BBE02, a putative restriction-modification gene product expressed by the linear plasmid lp25 (Kawabata et al., Infect. Immun.

Ixodes scapularis ticks (Acari: Ixodidae) from Louisiana are competent to transmit Borrelia burgdorferi, the agent of Lyme borreliosis.

The principal vector of Borrelia burgdorferi, the Lyme borreliosis spirochete, in the Northeast and Midwestern regions of the United States is the blacklegged tick Ixodes scapularis. Because of a favorable environment, I. scapularis is also plentiful in the South; however, a correlation with Lyme borreliosis cases does not exist in this region of the United States.

An immune evasion mechanism for spirochetal persistence in Lyme borreliosis.

Borrelia burgdorferi, the Lyme disease spirochete, persistently infects mammalian hosts despite the development of strong humoral responses directed against the pathogen. Here we describe a novel mechanism of immune evasion by B. burgdorferi.