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Publications (67)
Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other.
Material and methods
To investigate this, we used unbia...
Lyme disease, caused by Borrelia burgdorferi (Bb) infection, has a broad spectrum of clinical manifestations and severity. Patients with possible Lyme disease may seek out or be referred to rheumatologists. Today, the most common reason to engage a rheumatologist is due to complaints of arthralgia. After skin, neurologic manifestations of Lyme dise...
Lyme disease is a multisystem disorder primarily caused by Borrelia burgdorferi sensu lato. However, B. garinii, which has been identified on islands off the coast of Newfoundland and Labrador, Canada, is a cause of Lyme disease in Eurasia. We report isolation and whole-genome nucleotide sequencing of a B. garinii isolate from a cotton mouse (Perom...
Borrelia garinii , is a cause of Lyme disease in Europe and Asia. For the first time, we report it in the southeastern United States in rodents. Whole genome sequencing and phylogenetic analysis revealed that USA-located B. garinii is part of a clade consisting primarily of few European and majority of Far Eastern strains. Continued surveillance of...
Lyme disease is a tick-borne infection caused by the bacteria Borrelia burgdorferi . Current diagnosis of early Lyme disease relies heavily on clinical criteria, including the presence of an erythema migrans rash. The sensitivity of current gold-standard diagnostic tests relies upon antibody formation, which is typically delayed and thus of limited...
Lyme disease, caused by some Borrelia burgdorferi sensu lato, is the most common tick-borne illness in the Northern Hemisphere and the number of cases, and geographic spread, continue to grow. Previously identified B. burgdorferi proteins, lipid immunogens, and live mutants lead the design of canonical vaccines aimed at disrupting infection in the...
Borrelia burgdorferi was discovered to be the cause of Lyme disease in 1983, leading to seroassays. The 1994 serodiagnostic testing guidelines predated a full understanding of key B. burgdorferi antigens and have a number of shortcomings. These serologic tests cannot distinguish active infection, past infection, or reinfection. Reliable direct-dete...
Background:
With approximately one-third of their genomes consisting of linear and circular plasmids, the Lyme disease agent cluster of species has the most complex genomes among known bacteria. We report here a comparative analysis of plasmids in eleven Borreliella (also known as Borrelia burgdorferi sensu lato) species.
Results:
We sequenced t...
Borrelia miyamotoi, a relapsing fever-related spirochete transmitted by Ixodes ticks, has been recently shown to be a human pathogen. To characterize the prevalence of this organism in questing Ixodes ticks, we tested 2,754 ticks for a variety of tickborne pathogens by PCR and electrospray-ionization mass spectrometry. Ticks were collected from Cal...
Early Lyme disease is often difficult to diagnose. Left untreated, symptoms can last for many years leading to chronic health problems. Serological tests for the presence of antibodies that react to Borrelia burgdorferi antigens are generally used to support a clinical diagnosis. Due to the biologically delayed antibody response, serology is negati...
Lyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex. To reconstruct the evolution of B. burgdorferi s.l. and identify the genomic basis of its human virulence, we compared the genomes of 23 B. burgdorferi s.l. isolates from Europe and the United States, including B. burgdorfer...
The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To de...
Many organisms, such as insects, filarial nematodes, and ticks, contain heritable bacterial endosymbionts that are often closely related to transmissible tickborne pathogens. These intracellular bacteria are sometimes unique to the host species, presumably due to isolation and genetic drift. We used a polymerase chain reaction/electrospray ionizati...
To develop and evaluate a rapid and accurate assay involving PCR amplification and electrospray ionization mass spectrometry of nucleic acid extracts from whole blood samples for the detection of Dirofilaria immitis infection in dogs.
Whole blood nucleic acid extracts from 29 dogs experimentally infected with D immitis (and in which circulating D i...
Direct molecular tests in blood for early Lyme disease can be insensitive due to low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we have developed a sensitive strategy to both detect and genotype B. burgdorferi directly from whole blood collected during the initial patient visit. This strategy improved sensitivity by...
Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards...
It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Borrelia spielmanii, and Borrelia bissettii have been associated with Lyme disease. We report the complete genome sequences of B. valaisiana VS116, B. spielmanii...
How genomic diversity within bacterial populations originates and is maintained in the presence of frequent recombination is a central problem in understanding bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial agent of Lyme disease, consist of diverse genomic groups co-infecting single individual vertebrate hosts and t...
The DNA or cells for this strains can be obtained from Sherwood Casjens (Univ. of Utah, sherwood.casjens@path.utah.edu).
Recent reports showed many patients with chronic fatigue syndrome (CFS) harbor a retrovirus, xenotropic murine leukemia-related virus (XMRV), in blood; other studies could not replicate this finding. A useful next step would be to examine cerebrospinal fluid, because in some patients CFS is thought to be a brain disorder. Finding a microbe in the c...
Human Lyme disease is caused by a number of related Borrelia burgdorferi sensu lato species. We report here the complete genome sequence of Borrelia sp. isolate SV1 from Finland. This isolate is to date the closest known relative of B. burgdorferi sensu stricto, but it is sufficiently genetically distinct from that species that it and its close rel...
Neurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.
Pooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volun...
A forensic capability to help identify perpetrators and exclude innocent people should be an integral part of a strategy against terrorist attacks. Exercises have been conducted to increase our preparedness and response capabilities to chemical, biological, radiological, and nuclear (CBRN) terrorist attacks. However, incorporating forensic componen...
Borrelia burgdorferi is a causative agent of Lyme disease in North America and Eurasia. The first complete genome sequence of B. burgdorferi strain 31, available for more than a decade, has assisted research on the pathogenesis of Lyme disease. Because a single
genome sequence is not sufficient to understand the relationship between genotypic and g...
Knowledge of the entire protein content, the proteome, of normal human cerebrospinal fluid (CSF) would enable insights into neurologic and psychiatric disorders. Until now technologic hurdles and access to true normal samples hindered attaining this goal.
We applied immunoaffinity separation and high sensitivity and resolution liquid chromatography...
Burkholderia mallei (Bm), the causative agent of the predominately equine disease glanders, is a genetically uniform species that is very closely related to the much more diverse species Burkholderia pseudomallei (Bp), an opportunistic human pathogen and the primary cause of melioidosis. To gain insight into the relative lack of genetic diversity w...
Lyme disease, caused by various species of Borrelia, is transmitted by Ixodes ticks in North America and Europe. Studies have shown the genotype of Borrelia burgdorferi sensu stricto (s.s.) or the species of B. burgdorferi sensu lato (s.l.) affects the ability of the bacteria to cause local or disseminated infection in humans.
We used a multilocus...
Ticks harbor numerous bacterial, protozoal, and viral pathogens that can cause serious infections in humans and domestic animals. Active surveillance of the tick vector can provide insight into the frequency and distribution of important pathogens in the environment. Nucleic-acid based detection of tick-borne bacterial, protozoan, and viral pathoge...
Forensic science can be instrumental in providing investigative leads or clues to help identify the perpetrators, and those who are innocent, of a chemical, biological, radiological, or nuclear terrorist attack, as well as identify leads during infectious outbreaks or other public health threats. Because of a need to react quickly in exigent circum...
Microbial pathogens have evolved sophisticated mechanisms for evasion of host innate and adaptive immunities. PFam54 is the largest paralogous gene family in the genomes of Borrelia burgdorferi, the Lyme disease bacterium. One member of PFam54, the complement-regulator acquiring surface proteins 1 (BbCrasp-1), is able to abort the alternative pathw...
The chromosome for this strain has been deposited under the Whole Genome Shotgun project accession ABCY00000000. The DNA or cells for this strains can be obtained from Sherwood Casjens (Univ. of Utah, sherwood.casjens@path.utah.edu) or Benjamin J. Luft (SUNY at Stony Brook, bluft@notes.cc.sunysb.edu).
Background: We examinedglobal changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to different conditions which may be analogous to what the organism may experience in its life cycle. Methods: Multidimensional separation coupled with tandem mass spectroscopy was used in order to determine the entire array of protein...
A process for validation is essential in the development of methods that microbial forensics uses to generate reliable and defensible results. Law enforcement investigators need to re- spond quickly to the best leads to counter ever-increasing threats and will rely upon results generated from the analyses of any microbial forensic evidence to attem...
Anthrax receptor (ATR) shares similarities with molecules relevant to haematopoiesis. This suggests that anthrax proteins might bind to these mimicking molecules and exert non-specific haematopoietic effects. The haematopoietic system is the site of immune cell development in the adult. As such, ATR ligand, protective antigen (PA) and the other ant...
Burkholderia mallei is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microb...
Science can be part of an effective investigative response to a bioterrorism event or a biocrime by providing capabilities to analyze biological and associated signatures in collected evidence. Microbial forensics, a discipline comprised of several scientific fields, is dedicated to the analysis of evidence from such criminal acts to help determine...
Schutzer and colleagues give guidance for physicians who believe that one of their patients has been a victim of an act of bioterror or another biocrime.
We investigated the possibility that manifestations of Lyme disease in certain hosts, such as arthritis and carditis, may be autoimmunity mediated due to molecular mimicry between the bacterium Borrelia burgdorferi and self-components. We first compared amino acid sequences of Streptococcus pyogenes M protein, a known inducer of antibodies that are...
Abstract Arthropod bites and stings are capable of inflicting injury, inciting allergic reactions, and transmitting systemic disease. Members of the Hymenoptera order are of particular importance because they are nearly ubiquitous in nature, and their stings may cause life-threatening allergic reactions. Stings from bees, wasps, and ants produce a...
Markers for HIV-associated dementia (HAD) are needed for diagnosis and management. Specific antibodies to brain and immune complexes (IC) in the cerebrospinal fluid (CSF) are potential markers. CSF IC were found in 4 of 4 HAD patients, 2 of 2 AIDS-central nervous system (CNS) lymphoma patients with dementia, 0 of 1 AIDS-CNS lymphoma patient without...
Comparative genomics of closely related bacterial isolates is a powerful method for uncovering virulence and other important genome elements. We determined draft sequences (8-fold coverage) of the genomes of strains JD1 and N40 of Borrelia burgdorferi sensu stricto, the causative agent of Lyme disease, and we compared the predicted genes from the t...
Borrelia burgdorferi antibodies preferentially present in cerebrospinal fluid (CSF) were examined by differentially probing a B. burgdorferi expression library with CSF and sera from patients with neurologic Lyme disease. Several phage clones selectively reacted
with CSF, and these genes were then expressed in recombinant form and used to detect sp...
Combating bioterrorism is a challenge to all of us. To be proactive, the U.S. Government has formalized the discipline of "microbial forensics" to deter and attribute perpetrators of such acts. This Policy Forum describes the foundations of the microbial forensics program: the creation of a national bioforensics laboratory, a partnership laboratory...
The etiology of HIV-associated dementia (HAD) is still unknown although direct viral effects have not been supported. Although evidence supports a role for products of activated macrophages, other evidence suggested the possibility of associated autoimmune phenomena at least as a marker. In a blinded analysis, non-HIV-infected whole brain material...
Infection with Borrelia burgdorferi, the cause of Lyme disease, has been accompanied by a puzzling delayed antibody (Ab) response to B. burgdorferi antigens (Ags) including the abundant organism-specific outer surface proteins, such as the 31-kD OspA. In humans the response to nonspecific B. burgdorferi Ags has required 3-6 weeks. The response to O...
Lyme disease has emerged as a major infection with frequent neurologic manifestations. These manifestations probably reflect several predominantly indirect pathogenetic mechanisms and involve host, vector, and organism factors. With early diagnosis and appropriate antibiotic treatment, patients do well. Because culture is not reliable, diagnosis ha...
The allergist may frequently be involved with cases of Lyme disease. There are at least three reasons for this. First, the major symptom is often a rash that brings into the differential diagnosis several diseases that the allergist is likely to have expertise in; therefore, the allergist's role as a diagnostician is very important. The second reas...
Diagnosis of infection with Borrelia burgdorferi, the cause of Lyme disease (LD), has been impeded by the lack of effective assays to detect active infection.
To determine whether B. burgdorferi-specific immune complexes are detectable during active infection in LD.
Cross-sectional analysis of serum samples from 168 patients fulfilling Centers for...
Chronic fatigue syndrome (CFS) and Lyme disease often share clinical features, especially fatigue, contributing to concern that Borrelia burgdorferi (Bb), the cause of Lyme disease, may underlie CFS symptoms. We examined 39 CFS patients and 40 healthy controls with a Bb immune complex test. Patients and controls were nonreactive. Centers for Diseas...
To the Editor: The diagnosis of a new Lyme disease infection by conventional assays may be difficult in persons who have antibodies to or immunologic memory of Borrelia burgdorferi proteins. This was the case in a recipient of vaccine containing recombinant outer-surface protein A (OspA) of B. burgdorferi (Connaught).1 Analysis of the antibody and...
Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi (Bb). Neurological involvement is common in all stages. In vivo expression of Bb antigens (Ags) and the immune response to them has not been well investigated in the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and concomitant downregulation of...
To determine the potential of detection in CSF of specific Borrelia burgdorferi antigen, OspA, as a marker of infection in neurologic Lyme disease and compare this with the detection of antibody.
CSF from 83 neurologic patients in an area highly endemic for Lyme disease was examined prospectively for (1) OspA by antigen capture ELISA and Western bl...
Borrelia burgdorferi (Bb), the cause of Lyme disease, has appeared not to evoke a detectable specific antibody response in humans until long after infection. This delayed response has been a biologic puzzle and has hampered early diagnosis. Antibody to the abundant organism-specific outer surface proteins, such as the 31-kD OspA, has rarely been de...
We examined CSF for Borrelia burgdorferi antigens using antigen-capture ELISA and Western (immuno) blot. Antigen-capture ELISA was positive in 38 of 77 (49%) CSF samples obtained from neurologic patients with presumed B burgdorferi infection, compared with one of 34 (3%) CSF samples obtained from other neurologic disease controls who came from a re...
Lyme disease has as its hallmark erythema migrans. However, it is only present in about one half of the patients who contract this disease. In its absence, the diagnosis of Lyme disease may be difficult. It depends upon a compatible history of exposure and clinical signs and symptoms together with positive results of serologic testing. Unfortunatel...
Lyme disease, caused by infection with Borrelia burgdorferi, can affect those exposed to a vector tick. Pregnant women are no exception, and such infection places the fetus at risk. It is particularly important to recognize the disease early so that effective therapy may be instituted. Although the present patient had a favorable outcome, not all d...
We analyzed cerebrospinal fluid (CSF) from 32 patients with neurological symptoms and evidence of Borrelia burgdorferi infection (29 were seropositive as determined by enzyme-linked immunosorbent assay, 2 were cell-mediated immune positive, and 1 had been seropositive as shown by enzyme-linked immunosorbent assay 9 months previously). CSF immune co...
To find out whether apparent seronegativity in patients strongly suspected of having Lyme disease can be due to sequestration of antibodies in immune complexes, such complexes were isolated and tested for antibody to Borrelia burgdorferi. In a blinded analysis the antibody was detected in all 10 seronegative Lyme disease patients with erythema chro...
Three patients with chronic polyneuropathy of unknown origin were found to have abnormalities in humoral immunity characterized by anti-nerve antibodies, cold-reactive anti-lymphocyte antibodies, and circulating immune complexes. In two patients, clinical improvement coincided with plasmapheresis and removal of the anti-nerve antibodies. Certain pa...
The Raji cell assay to detect immune complexes has been modified to a microtiter ELISA system. Raji cells were fixed to microplate wells, then reacted with serum samples or aggregated human IgG. Horseradish peroxidase-conjugated anti-human IgG was used to detect bound complexes. There was a linear relationship between aggregated IgG added and optic...
We investigated whether serologic evidence of lymphadenopathy-associated virus (LAV), an exogenous human T-cell lymphotropic and cytopathic retrovirus, correlated with the acquisition and transmission of the acquired immunodeficiency syndrome (AIDS). Serum from 17 of 25 patients with AIDS contained circulating IgG anti-LAV antibody (all of 5 adults...
