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Lewis, Kim

Kim Lewis, PhD
University Distinguished ProfessorLewis
Director, Antimicrobial Discovery Center
Northeastern University
Boston, MA
https://web.northeastern.edu/adc/

Developing Therapies for Treating Lyme Disease

Kim Lewis is a University Distinguished Professor and Director, Antimicrobial Discovery Center at Northeastern University in Boston, and a Fellow of the American Society of Microbiology. He obtained his Ph.D. in Biochemistry from Moscow University in 1980, and has been on the Faculty of MIT, University of Maryland, and Tufts University prior to coming to Northeastern.

Dr. Lewis has authored over 100 papers and is an inventor on several patents. His more notable findings include the development of general methods to grow previously uncultured bacteria that make up >99% of biodiversity on the planet, the discovery of the culprit of recalcitrant biofilm infections, drug-tolerant persister cells; and antimicrobials for sterilizing biofilm infections and killing M. tuberculosis.

Dr. Lewis presented over 90 invited talks. Dr. Lewis has been a permanent member of the Drug Discovery and Drug Resistance NIH Study Section, and Chair of two NIH Study Sections on Drug Discovery. Dr. Lewis has served as a panelist and contributor to the National Academies Institute of Medicine reports on antibiotic resistance in 2010, 2011 and 2014, and the European Academies Science Advisory Meeting in 2014. Dr. Lewis is a member of Faculty 1000, a world-wide panel of experts evaluating research advancements. He is a recipient of the MIT C.E. Reed Faculty Initiative Award for an innovative research project (1992), and is a recipient of the NIH Director’s Transformative Grant (2009).

Apart from his work in Academia, Dr. Lewis has served as a consultant to the Pharmaceutical Industry, The Biotech, and is a founder of two Biotech Companies, NovoBiotic Pharmaceuticals, and Arietis Corporation.


Conference Lecture Summary

The nature of Post-Treatment Lyme Disease Syndrome (PTLDS) remains unknown, but it is reasonable to assume that minimizing the duration of an acute infection will diminish if not prevent the chronic form of the disease. With this in mind, we set out to identify antimicrobials that efficiently kill Borrelia burgdorferi. This led to the identification of two experimental compounds. One is disulfiram, an FDA approved drug for treating alcoholism that eradicates persisters of B. burgdorferi and acts selectively against the pathogen. We developed a stable formulation of disulfiram that is effective in a mouse model of Lyme disease. If the pathogen is present at the chronic stage, disulfiram is also expected to clear it. The other compound is a natural product selective against B. burgdorferi. An aberrant microbiome is known to contribute to a number of autoimmune diseases, and patients with PTLDS exhibit changes in the microbiome as well. This suggests microbiome restoration, and using antibiotics that do not harm gut symbionts.




Spector, Neil

Neil Lee Spector, MDSpector
Associate Professor of Medicine
Sandra Coates Associate Professor
Associate Professor of Pharmacology & Cancer Biology
Member of the Duke Cancer Institute
Durham, NC
https://medicine.duke.edu/faculty/neil-lee-spector-md

Applying the Lessons From Cancer Research to the Diagnosis and Treatment of TBD

Dr. Neil Spector completed a medical oncology-hematology and bone marrow transplant fellowships at Massachusetts General Hospital and Dana-Farber Cancer Institute, Harvard Medical School, where he remained on the faculty as an attending physician, pursuing his research on the molecular events that promote the switch from a normal to malignant cells. From 1998 through 2006, Dr. Spector directed the Translational Oncology Research Program at GlaxoSmithKline where his innovative bench to bedside strategy is credited with leading to FDA approval of two molecularly targeted therapies, (i) nelarabine, an ara-G prodrug approved for the treatment of pediatric T-cell acute lymphoblastic leukemia; and (ii) lapatinib, the only small molecule inhibitor of the EGFR and HER2 tyrosine kinases currently approved for the treatment of HER2 overexpressing breast cancer. His application of translational research to the preclinical and clinical development of lapatinib remains an example of how precision oncology can transform treatment of cancer patients, and facilitate the development of targeted cancer therapies. In 2006, Dr. Spector joined the faculty at Duke University School of Medicine where he is currently the Sandra Coates Associate Professor Medicine. His research focuses on elucidating molecular mechanisms of therapeutic resistance to targeted therapies and strategies to prevent and/or overcome resistance, and more recently, the design of targeted strategies to block specific steps in the earliest stages of cancer development. He was selected by his peers as a Komen Research Scholar, a group representing the top 50 breast cancer researchers from around the world. In addition to his research, Dr. Spector continues to see oncology patients and was recently appointed National Director of Precision Oncology for the VA Healthcare System. Dr. Spector also detailed his personal journey with Lyme disease and the life-threatening cardiac complications that ensued in his recent book, Gone In a Heartbeat: A Physician’s Search for True Healing.


Conference Lecture Summary:

There are striking similarities in the pathogenesis of many cancers and Borrelia infection. The insights that have been made in understanding tumorigenesis and cancer progression and metastatic dissemination have led to paradigm shift in drug development, from the historical reliance on cytotoxic chemotherapies to small molecules targeting oncogenic driver mutations and immunotherapies designed to activate antitumor immune responses. The latter targeted therapies have transformed clinical outcomes for many patients with solid tumor and hematological malignancies. In this presentation, I will discuss how the successful lessons learned in cancer biology and targeted/immunotherapy drug development may apply to the way think in terms of new, non-antibiotic therapies for Borrelia and other tick-borne illnesses. I will discuss an ongoing collaborative project in our lab and others to utilize a platform technology that has successfully identified novel small molecule therapies for cancer, metabolic and certain infectious diseases, to identify a new class of molecularly targeted therapies for Borrelia.




Oaklander, Anne Louise

OaklanderAnne Louise Oaklander, MD, PhD
Associate Professor of Neurology
Harvard Medical School
Assistant in Neurology and Neuropathology at Massachusetts General Hospital
Director of Massachusetts General Hospital’s Nerve Unit Group.
Boston, MA
https://www.massgeneral.org/doctors/doctor.aspx?id=17253#
NeuropathyCommons.org

Small-Fiber Peripheral Neuropathy: A Pathway for Some Patients

Dr. Oaklander, Associate Professor of Neurology at Harvard Medical School and Assistant in Neurology and Neuropathology at Massachusetts General Hospital, directs MGH’s Nerve Unit group. After undergraduate studies at Columbia and Cornell she received M.D. and Ph.D. degrees (neuroscience) from Albert Einstein College of Medicine. She completed neurology residency at Rutgers, fellowships in peripheral nerve and neurosurgery at Johns Hopkins, then joined Hopkins’ faculty. At Harvard she directs the federally-funded Nerve Unit research team that identified the causes of chronic pain after shingles and limb injuries. They discovered a new small-fiber polyneuropathy that causes disabling multi-symptom illnesses in young people, and that small-fiber polyneuropathy underlies 40% of fibromyalgia cases. They proposed that some small-fiber neuropathies are autoimmune and demonstrated efficacy of immunotherapy (IVIg). She has more than 100 publications and serves on editorial boards of professional journals. A Fellow of the American Academy of Neurology and the American Neurological Association, her research has been profiled in Science, Scientific American Mind, and by PBS. She is listed in America’s Top Doctors, America’s Top Physicians, and US News and World Report. She serves on NIH’s Research Council and has served on panels for the NIH, the FDA, and the Institute of Medicine.


Conference Lecture Summary:

Our research team investigates biological causes of unexplained sensory and other symptoms.  We have studied unexplained multisymptom illnesses that include chronic widespread pain, itching, dizziness on standing and rapid heartbeat (POTS), and gastrointestinal symptoms.  In some but not all clinical patients and research subjects, we find objective evidence suggesting that small-fiber polyneuropathy (SFPN) may be part of the problem. The strongest studies so far are for fibromyalgia. Our lab and others around the world have published that about 40% of fibromyalgia patients have skin biopsies and other neurological evidence of SFPN. For them, we recommend the standard blood tests to look for potentially treatable causes or contributors, especially smoking and diabetes, and then medical treatment targeting their own problem.  We have helped identify disease-specific treatments for genetic and autoimmune types of SFPN.  We provide non-commercial information for the public at https://neuropathycommons.org/ and in a public lecture at Radcliffe posted at https://www.youtube.com/watch?v=s66LvWQ5Qso.




Occi, James

James L. Occi, PhD (candidate)Occi
Research Teaching Specialist RNJMS
Center for Vector Biology, Department of Entomology Rutgers University
Newark, NJ

The Discovery of the “Asian long-horned tick,” Haemaphysalis longicornis, in New Jersey: A Combination of Perseverance, Luck and the Joy of Tick Collecting”

James (Jim) Occi is a microbiologist who has been involved in searching for new antibiotic entities for almost 30 years. He has done research in big pharma for over 20 years and continues this endeavor as a research microbiologist at New Jersey Medical School in the Department of Emerging Pathogens (Newark).  Jim is pursuing his PhD at Rutgers University at the Center for Vector Biology (New Brunswick) and wants to be a medical entomologist when he grows up. For his thesis, Jim is studying tick-borne diseases in New Jersey tick populations under the direction of Dr. Dina Fonseca. He has a BS and MA in Biology from Montclair State University and an MS in Microbiology from Seton Hall University.


Conference Lecture Summary

In November 2017 the USDA confirmed an infestation of the longhorned tick (Haemaphysalis longicornis) on a sheep in Hunterdon County, New Jersey. This tick is indigenous to parts of China, Korea and Japan where it typically feeds on cattle.  I will summarize the latest on where the longhorned tick has been found in the US and discuss ongoing research on its ecology, life cycle and possible involvement in transmission of tick-borne pathogens.




Pal, Utpal

Utpal Pal, PhD
Utpal
Professor & Director, VMSC Graduate Program
Veterinary Medicine
University of Maryland
College Park , MD
https://vetmed.umd.edu/about/faculty/utpal-pal
https://agnrfacultystaff.umd.edu/upal

Immune Evasion of Lyme Disease Agents

Dr. Utpal Pal, PhD, is a Professor and Director of Veterinary Medical Sciences graduate program at the University of Maryland, College Park. For more than two decades, Pal laboratory is studying the molecular mechanisms of microbial persistence, pathogenesis, vector biology and transmission events relevant to Lyme disease. This multi-system infection in human is caused by an atypical group of bacterial pathogens, Borrelia burgdorferi sensu lato, which are transmitted by Ixodes ticks. Dr. Pal’s studies over the past decades have contributed in identifying the biological significance of several B. burgdorferi virulence determinants, roles of host or vector molecules in microbial pathogenesis and/or host-pathogen interaction as well as developing functional genomics and gene manipulations tools in Lyme borreliosis research. More recent discoveries from Pal laboratory included a recently identified interferon-like defense response in ticks as well as a novel immune evasion mechanism of B. burgdorferi. Collectively, these studies seek to contribute to the development of novel preventive and therapeutic interventions against serious illnesses that is highly prevalent in the globe.

To date, Dr. Pal has trained 10 doctoral students, 21 post-doctoral fellows and six junior/sabbatical faculty members in his laboratory — the majority of whom are engaged in various scientific and academic careers, including leadership positions. For the past two years, he is serving as the Director of Veterinary Medical Sciences Graduate program and an Investigator/Mentor on NIH training grants in the campus. Dr. Pal has authored more then 80 peer-reviewed research articles, and edited one book and four book chapters on B. burgdorferi. He has presented over 25 invited presentations on various aspects of Lyme disease and contributed as guest editor or editorial board members for seven journals. Research studies in Dr. Pal’s laboratory are funded by multiple sources, including Federal, State, Private organizations and Pharmaceutical Industry.


Conference Lecture Summary

Borrelia burgdorferi and related spirochetes cause Lyme disease, a prevalent tick-borne zoonosis. The pathogen displays a remarkable evolutionary divergence from other bacteria and thus it is perhaps not surprising that the vast majority of the B. burgdorferi genome encodes proteins of yet unknown functions. To advance our knowledge of microbial pathogenesis, we have characterized a select set of structurally unique B. burgdorferi gene-products that act as novel virulence determinants and support spirochete infection. Our most recent studies uncovered a unique innate immune evasion strategy of B. burgdorferi that is orchestrated by one of its cell surface proteins of unknown function, annotated as BBA57. We show the protein is highly induced during early mammalian infection and supports microbial persistence via evasion of a plethora of host microbicidal response. We also discovered a remarkable plasticity in such spirochete immune evasion strategy as even in its absence, B. burgdorferi still able to adapt and establish long-term infection. Understanding the fundamentals of spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel approaches to combat highly-prevalent vector-borne infections like Lyme borreliosis.




Naviaux, Robert

NaviauxRobert K. Naviaux, MD, PhD
Professor of Medicine, Pediatrics, Pathology, and Genetics
The Mitochondrial and Metabolic Disease Center
University of California, San Diego School of Medicine
San Diego, CA
naviauxlab.ucsd.edu
biochemgen.ucsd.edu

Metabolomic Features of Chronic Illness—Lessons from Gulf War Illness and Chronic Fatigue Syndrome

Dr. Naviaux is the founder and co-director of the Mitochondrial and Metabolic Disease Center (MMDC), and Professor of Medicine, Pediatrics, Pathology, and Genetics at UCSD. He directs a core laboratory for metabolomics at UCSD. He is the co-founder and a former president of the Mitochondrial Medicine Society (MMS), and a founding associate editor of the journal Mitochondrion. He is an internationally known expert in human genetics, inborn errors of metabolism, metabolomics, and mitochondrial medicine. Dr. Naviaux is the discoverer of the cause of Alpers syndrome—the oldest Mendelian form of mitochondrial disease—and the developer of the first DNA test to diagnose it. His lab also discovered the first mitochondrial DNA (mtDNA) mutations that cause genetic forms of autism and the metabolic features of the cell danger response (CDR). He directed the first FDA-approved clinical trial to study the safety and efficacy of the antipurinergic drug suramin as a new treatment for autism spectrum disorder (ASD). His development of new methods in metabolomics showed that several complex chronic disoreders like ASD and chronic fatigue syndrome (ME/CFS) have a metabolic signature that can be used in diagnosis and lead to fresh insights to treatment.


Conference Lecture Summary

Metabolomics has emerged as a powerful new tool in systems biology. We have collected data on over 600 natural metabolites in 8 different chronic disease cohorts by broad-spectrum, targeted metabolomics using hydrophilic interaction liquid chromatography electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS), or LC-MS/MS for short. These studies have included autism spectrum disorder (ASD), post-traumatic stress disorder (PTSD) with and without traumatic brain injury (TBI), Gulf War Illness (GWI), major depressive disorder (MDD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), primary sclerosing cholangitis (PSC), the response to endurance and resistance exercise, and natural aging. In addition, we have studied mouse models and the developmental state known as dauer in the worm, C. elegans. These studies have shown that a diagnostic metabolic signature is present in every chronic illness studied to date, and that strong gender differences are present in each disease. All chronic illnesses that last more than about 6 months were found to express the metabolic features of a universal cellular response to environmental stress called the cell danger response (CDR). The CDR is comprised of a choreographed sequence of cellular metabolic transitions that must be completed as part of an evolutionarily conserved healing cycle. Chronic illness results when the healing cycle is blocked at different stages by abnormal metabokine signaling. Metabokines are signlaing molecules like ATP, butyrate, succinate, α-ketoglutarate, long chain fatty acids, eicosanoids, and sphingolipids that are natural products of metabolism inside of cells, but bind to specific G-protein coupled receptors (GPCRs) and ionotropic receptors outside of the cell. The relevance of these findings for post-treatment Lyme disease syndrome (PTLDS) will be discussed.




Szantyr, Beatrice

SzantyrBeatrice M. Szantyr, MD, FAAP
Internal Medicine
Pediatrics and Adolescent Medicine

Lincoln, ME

Lyme Disease – An Ounce of Prevention: Survey of the Evidence for Prevention Strategies in Lyme Disease

Dr. Beatrice Szantyr, a fellow of the American Academy of Pediatrics and member of the American College of Physicians, has been board certified in both internal medicine and pediatrics. She received her undergraduate degree from Fordham University, her doctorate in medicine from the University of Connecticut School of Medicine, and completed her internship and residency in Internal Medicine, Pediatrics and Adolescent Medicine at St. Louis University Hospitals and Cardinal Glennon Memorial Hospital for Children. She made her way to Maine over 30 years ago in fulfillment of a National Health Service Corps commitment. Through her private Medicine and Pediatrics practice in rural Maine she has provided a broad range of clinical services in a variety of settings for people of all ages. Her current professional activities are focused in education.

Dr. Szantyr has lectured on Lyme disease and related tick-borne disorders throughout Maine and New England to both professional and community groups. She is an active member of Maine CDC’s Vector Borne Disease Work Group as well as the International Lyme and Associated Diseases Society, serving on the provider education working group to develop and present the full day evidence-based course: The Fundamentals of Lyme Disease. She is the medical advisor for MaineLyme, a Maine-based non-profit formed in 2010 and dedicated to decreasing the occurrence of Lyme and related tick-borne diseases in Maine through awareness, prevention, education and advocacy.


Conference Lecture Summary

The increasing number of cases of Lyme disease as well as the spread of Lyme disease into previously non-endemic areas have been well documented. Environmental and other factors that contribute to this expansion continue to be evaluated. Early diagnosis and treatment have been shown to be effective in many cases. But not every case is recognized early. Of the cases confirmed by CDC over a 15 year period, 30% did not have a history of the most recognizable early sign/symptom of the illness: the EM rash. The consequences of missed and delayed diagnosis and treatment of Lyme disease are significant. All of these elements make prevention an important consideration.

Many common-sense measures have been proposed over the years for the prevention of Lyme disease, though often without much evidence of efficacy. Several levels of prevention have evolved to have a larger body of evidence supporting their use. These measures range from the immediate failsafe of Ixodes tick bite management strategies to personal protection measures and host and property management, vaccine development for humans and host animals, and wider integrated pest management strategies that combine many of these individual measures in a more comprehensive approach to this important public health issue.

This presentation will present a survey of prevention approaches and the evidence supporting their implementation.

 




Ben Mamoun, Choukri

BenMamounChoukri Ben Mamoun, PhD
Associate Professor
Department of Internal Medicine & Department of Microbial Pathogenesis
Section of Infectious Diseases
Yale School of Medicine
New Haven, CT
https://medicine.yale.edu/micropath/people/choukri_benmamoun-2.profile

Targeting the Achilles Heel of Babesia Parasites’ Mode of Survival Within Human Red Blood Cells

Choukri Ben Mamoun is an Associate Professor at Yale with a primary appointment in the Department of Internal Medicine and a secondary appointment in the Department of Microbial Pathogenesis. He received his PhD in 1996 in Molecular Microbiology in France from University of Paris XI and Institut National Agronomique Paris-Grignon. In 1996, he joined the Department of Molecular Microbiology at Washington University as a Research Fellow of the Howard Hughes Medical Institute and in 2000 became a faculty member at University of Connecticut Health Center. In 2009, he joined the faculty at the Yale School of Medicine as a Principal Investigator with a focus on the biology and therapy of the protozoan parasites that cause human malaria and babesiosis.

Dr. Ben Mamoun has authored 78 peer-reviewed papers in the field of eukaryotic pathogenesis. Among his important findings in the malaria field are: the development of selectable markers for genetic manipulation of P. falciparum (Mamoun et al., PNAS 1999), discovery of a novel metabolic pathway for lipid metabolism in P. falciparum (Pessi et al, PNAS 2004), creation of the first conditional knockouts of P. falciparum lacking the purine transporter or phosphoethanolamine methyltransferase (El Bissati et al., PNAS 2006 and Witola et al., JBC 2007), discovery of lipid regulation as a critical step in P. falciparum sexual differentiation (Bobenchik et al., PNAS 2013). His notable findings in the babesiosis field are: Discovery of a new combination therapy consisting of atovaquone and endochin-like quinolone (ELQ-334) for radical cure of babesiosis infection in mice (Lawres et al., J. Exp. Med, 2016) and the development of a new diagnostic test for detection of B. microti active infection (Thekkiniath et al., J. Clin. Microb. 2018).

Dr. Ben Mamoun has served as a member or chair of several NIH and DOD study sections and other international organizations. He has served on the editorial board of several research journals, presented seminars and lectures both nationally and internationally and received multiple awards including the Patterson Award, the Burroughs Welcome Award and the Bill and Melinda Gates Foundation Award.

In addition to his academic program, Dr. Ben Mamoun is the founder of a biotech company, ELIV5 Therapeutics.


Conference Lecture Summary

Since the completion of the assembly and annotation of the genome of the human pathogen Babesia microti, my laboratory has been involved in the development of novel approaches to detect active babesia infection and discovery of more effective therapies to treat human babesiosis. In this lecture, I will present new data showing that B. microti uses a novel mechanism for delivery of proteins into the host, and how we exploited this information to develop a highly sensitive assay for detection of B. microti active infection in human and mouse blood. Furthermore, I will present our recent discovery of a new combination therapy that targets a critical step in B. microti metabolism during its development within mouse and human red blood cells and results in radical cure of the disease.




Flegr, Jaroslav

Jaroslav Flegr, PhDjfsmall1
Professor of Ecology and Associate Professor of Parasitology
National Institute of Mental Health
Klecany, Czechia
Faculty of Science, Charles University
Prague, Czechia

The Effect of Pet-Transmitted Diseases on the Mental and Physical Health of the General Population

Jaroslav Flegr is an evolutionary biologist and evolutionary psychologist affiliated to Fac. of Science
Charles University and National Institute of Public Health, Czechia. He is a discoverer of effects of latent
toxoplasmosis and Rh factor on human behavior and mental and physical health, as well as an author of
theories of frozen plasticity and frozen evolution. He has published four books and about 150 research
articles.


Conference Lecture Summary

Cross-sectional studies showed that being injured by a cat correlates with symptoms of impaired mental
health, such as depressiveness, the probability of being diagnosed with major depression, and also with
the occurrence of many physical health problems. Cat scratch disease, the infection with the
bacterium Bartonella henselae, was suggested to be responsible for these associations. We have
recently found that the situation can be more complicated and that other pathogens transmitted from cats
can be responsible for the associations




Platts-Mills, Thomas A.

Platts MillsThomas A. Platts-Mills, PhD, FRS
Professor of Medicine and Microbiology
Chief, Division of Asthma, Allergy & Immunology
University of Virginia School of Medicine
Charlottesville, VA
https://med.virginia.edu/asthma-allergy-immunology/faculty-fellows/meet-the-chief/

Sensitization to Alpha-gal as a Consequence of Lone Star Tick Bites

Thomas Platts-Mills is Professor of Medicine and Microbiology at the UVA School of Medicine. The son of a British member of parliament, he was educated at Balliol College, Oxford, and received his medical training at St. Thomas’ Hospital Medical School in London. He earned a PhD from London University and completed a fellowship at Johns Hopkins University under the tutelage of Kimishige Ishizaka. He has been a member of Britain’s Royal College of Physicians since 1971.

Dr. Platts-Mills joined UVA’s faculty in 1982, and has served as chief of the Allergy division since 1993. He has also served a term as president of the American Academy of Allergy, Asthma, and Immunology (AAAAI).

In 2010, Dr. Platts-Mills was elected a Fellow of the Royal Society for his research into the causes of asthma and allergic disease. The Royal Society is the United Kingdom’s national academy of science and the oldest scientific academy in the world. Only a small number of fellows are physicians, and Platts-Mills is the first allergist ever elected. His election was based on more than 30 years of research on the role that dust mite, cat and cockroach allergens play in the development of allergic disease and asthma.


Conference Lecture Summary

In large areas of the United States, the lone star tick Amblyomma americanum has increased dramatically because of the increase in the deer population which is the primary breeding host for this tick. The lone stars are known vectors for several diseases, but recently it has been shown that bites from larval or adult ticks can induce sensitization to an important oligosaccharide of the non-primate mammals. This sensitization can be
identified by an in vitro assay for IgE to galactose alpha-1, 3-galactose (alpha-gal.) The presence of this antibody was first recognized because of severe reactions to the monoclonal antibody cetuximab. However, equally significant, it is now clear that sensitized subjects can experience delayed anaphylaxis 2-5 hours after eating red meat. This form of delayed reactivity was initially difficult to diagnose. It is now clear that the combination of reactions starting in adult life, the characteristic delay after eating red meat and a positive blood test, is sufficient to diagnose the condition. Furthermore, in these cases a diet avoiding red meat is effective in 90% of cases in preventing further severe attacks. Strikingly, bites of these ticks that are related to sensitization produce severe and prolonged itching at the site, which is very different from the experience with bites from Ixodes scapularis. Although the lone star tick routinely carries Rickettsia amblyomii, there is very little evidence that the sensitization to the oligosaccharide is caused by symbionts.