scholarly journals Proteomic Analyses of Morphological Variants ofBorrelia burgdorferiShed New Light on Persistence Mechanisms: Implications for Pathogenesis, Diagnosis and Treatment

2018 ◽  
Author(s):  
Jie Feng ◽  
Ying Zhang
Keyword(s):  
Lyme Disease ◽  
Stationary Phase ◽  
Cell Envelope ◽  
The United States ◽  
Planktonic Form ◽  
Vector Borne ◽  
Morphological Variants ◽  
Mechanisms Of Persistence ◽  
Related Proteins ◽  
Shed Light

AbstractBorrelia burgdorfericauses Lyme disease, which is the most common vector borne disease in the United States and Europe. Although 2-4 week antibiotic treatment for Lyme disease is effective in the majority of cases, about 10–20% patients suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the mechanisms of PTLDS are unclear, persisting organisms not killed by current Lyme antibiotics has been suggested as a possible explanation.B. burgdorferican spontaneously develop different morphological variant forms under stress or in stationary phase with increased persistence to antibiotics. To shed light on the possible mechanisms by which these variant forms develop persistence, here, we isolated threeB. burgdorferiforms, log phase spirochetal form, stationary phase planktonic form, and stationary phase aggregated biofilm-like microcolony form. We showed that the two separated stationary phase forms especially microcolony form have more persistence to antibiotics than the log phase spirochetal form. Then, we performed mass spectrometry (MS/MS) analysis to determine the proteomic profiles of the three different forms to reveal the mechanisms of persistence inB. burgdorferi. We identified 1023 proteins in the threeB. burgdorferiforms, with 642 proteins (63%) differentially expressed. Compared with the log phase spirochetal form ofB. burgdorferi, a total of 143 proteins were upregulated in both stationary phase planktonic form and microcolony form. Among these common upregulated proteins, 90 proteins had predicted functions and were mapped to different pathways involved in infection and virulence, DNA repair, heat shock, transport, sporulation, cell envelope and metabolism, many of which are consistent with persister mechanisms in other bacteria. A particularly interesting observation is that infection and virulence related proteins are highly up-regulated in stationary phase planktonic form and microcolony form compared with log phase spirochetal form. These findings shed new light on the mechanisms ofB. burgdorferipersistence and offer novel targets for developing more effective diagnostics, vaccines and treatments.

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

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 542 ◽  
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.

scholarly journals Recent Progress in Lyme Disease and Remaining Challenges

2021 ◽  
Vol 8 ◽  
Author(s):  
Jason R. Bobe ◽  
Brandon L. Jutras ◽  
Elizabeth J. Horn ◽  
Monica E. Embers ◽  
Allison Bailey ◽  
...  
Keyword(s):  
United States ◽  
Lyme Disease ◽  
Molecular Mechanisms ◽  
The United States ◽  
Persistent Symptoms ◽  
Number Of Patients ◽  
Vector Borne ◽  
The Many ◽  
Long Term Impact ◽  
Patients Experience

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

The Limping Child: Could It Be Lyme Arthritis? Information and Planning for School Nurses

2019 ◽  
Vol 34 (5) ◽  
pp. 262-265
Author(s):  
Tanya Laudenslager ◽  
Sheila Q. Hartung
Keyword(s):  
Lyme Disease ◽  
Joint Pain ◽  
School Setting ◽  
The United States ◽  
School Nurses ◽  
Lyme Arthritis ◽  
Acute Injury ◽  
Vector Borne Disease ◽  
History Of ◽  
Vector Borne

Lyme disease is the most common vector-borne disease in the United States with Lyme arthritis becoming one of the most common symptoms of Lyme disease. It is imperative that school nurses become familiar with vector-borne disease and promptly consider Lyme arthritis to be contemplated as a differential diagnosis of a child presenting to the office with a limp and joint pain and swelling with no history of acute injury. The following article will discuss the overview, implications and management of Lyme arthritis in the school setting and includes a relevant IHP for school nurses to utilize in practice.

scholarly journals Lyme Disease and Pregnancy

1995 ◽  
Vol 3 (6) ◽  
pp. 256-261 ◽  
Author(s):  
James M. Alexander ◽  
Susan M. Cox
Keyword(s):  
Lyme Disease ◽  
Clinical Course ◽  
Transmission Rate ◽  
Pregnant Patient ◽  
The United States ◽  
Prompt Treatment ◽  
Clinical Presentations ◽  
Vector Borne ◽  
Harmful Effects ◽  
In Pregnancy

Lyme disease is the most commonly transmitted vector-borne disease in the United States, with many regions of the country at risk. Like other spirochete-borne infections, Lyme disease progresses in stages, making diagnosis in the early stages of the illness and prompt treatment important for cure. An early diagnosis is made difficult by the less-than-ideal serologic tests and the varied clinical presentations of the disease. Although Lyme disease has been reported in pregnancy, the transmission rate to the fetus and potential harmful effects are largely unknown. This review discusses the diagnosis, clinical course, and treatment of Lyme disease with an emphasis on the pregnant patient.

scholarly journals Assessing Recognition of the Vector of Lyme Disease Using Resin-Embedded Specimens in a Lyme Endemic Area

2020 ◽  
Author(s):  
Gebbiena M Bron ◽  
Hannah Fenelon ◽  
Susan M Paskewitz
Keyword(s):  
United States ◽  
Lyme Disease ◽  
Adult Female ◽  
Endemic Area ◽  
Ixodes Scapularis ◽  
The United States ◽  
Convenience Sample ◽  
Potential Benefits ◽  
Vector Borne ◽  
Tick Check

Abstract Lyme disease (LD) is the most common vector-borne disease in the United States. To assess whether a tick bite puts someone at risk for LD, adequate tick identification skills are needed. We surveyed residents of a high LD-incidence state, Wisconsin, on their ability to distinguish ticks from insects and to identify the specimens that could transmit the LD causative agent. Surveys were conducted using resin blocks with four insects and four tick specimens embedded. About half of the participants (64 of 130) recognized all of the ticks, and 60% of those individuals chose only ticks and no insects. Younger participants (18- to 44-yr old) were more likely to identify ticks correctly compared with those 45 yr and older. Participants who agreed strongly with the statement ‘I know a lot about ticks` were also likelier to correctly identify ticks. When asked to identify which specimens could transmit LD, less than 25% of participants chose both the Ixodes scapularis Say adult female and nymph and about half of those (15% of participants) picked only those two and no other specimens. Although the relatively small convenience sample was biased toward younger participants who consider themselves ‘outdoorsy’, results showed that further assessments of tick recognition skills are needed to understand what determines whether people can recognize medically important ticks and to evaluate the potential benefits of enhanced education. In addition to the value of the resin blocks as research tools, the blocks may be useful as training tools to improve tick check efficacy.

scholarly journals Immune Mediators of Murine Lyme Arthritis

2014 ◽  
Author(s):  
◽  
Anna Maria Cunningham
Keyword(s):  
Lyme Disease ◽  
Subsequent Development ◽  
The United States ◽  
Lyme Arthritis ◽  
Immune Mediators ◽  
Eicosanoid Production ◽  
Immunological Mechanisms ◽  
Serum Transfer ◽  
Dietary Fish ◽  
Vector Borne

Lyme disease is the most common vector-borne disease in both the United States and Europe; however, its pathogenesis is incompletely understood. The studies described in this thesis aid in the elucidation of mechanisms regulating murine Lyme arthritis and may suggest mechanisms by which human Lyme disease is mediated. (1) We found that the chemokine KC is responsible for neutrophil recruitment and subsequent development of Lyme arthritis and carditis. This was the first study to describe an immunological regulatory mechanism mediating disease susceptibility to murine Lyme disease, as resistant mice (B6) produce less KC than susceptible (C3H/HeJ) mice and do not develop disease. (2) We found that metabolites produced via the COX-2 pathway are important for functional resolution and that resolution is likely mediated via the PGE2/EP2 axis. (3) We found that although dietary fish oil substitution leads to a global shift in eicosanoid production (from AA/LA-derived eicosanoids to EPA/DHA-derived eicosanoids) and promotes antiinflammatory prostaglandin production, disease severity is not altered. (4) We found that eicosanoid production throughout the course of autoantibody-drive K/BxN serum-transfer arthritis differs significantly from that seen during Lyme arthritis and that patterns of eicosanoid expression reflect the severity and kinetics of each type of arthritis. These studies aid in understanding the immunological mechanisms regulating the occurrence and severity of murine Lyme arthritis.

scholarly journals Activity of Sulfa Drugs and Their Combinations against Stationary PhaseB. burgdorferiin vitro

2017 ◽  
Author(s):  
Jie Feng ◽  
Shuo Zhang ◽  
Wanliang Shi ◽  
Ying Zhang
Keyword(s):  
Lyme Disease ◽  
Stationary Phase ◽  
Relative Activity ◽  
Positive Control ◽  
Drug Combinations ◽  
Sulfa Drugs ◽  
Sulfa Drug ◽  
The Us ◽  
Vector Borne

AbstractLyme disease is a most common vector borne disease in the US. Although the majority of Lyme patients can be cured with the standard 2-4 week antibiotic treatment, at least 10-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library onB. burgdorferiand found some drug hits including sulfa drugs as having good activity againstB. burgdorferistationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities againstB. burgdorferistationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phaseB. burgdorferienriched in persisters, however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations againstB. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four drug combinations dapsone+minocycline+cefuroxime+azithromycin and dapsone+minocycline+cefuroxime+rifampin showed best activity against stationary phaseB. burgdorferiin these sulfa drug combinations. However, these 4-sulfa drug containing combinations still had considerably less activity againstB. burgdorferistationary phase cells than the daptomycin+cefuroxime+doxycycline used as a positive control which completely eradicatedB. burgdorferistationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinationsin vitroand also in animal models.

scholarly journals Lyme Disease Presenting with Multiple Cranial Nerve Deficits: Report of a Case

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Abhishek Chaturvedi ◽  
Keith Baker ◽  
Donald Jeanmonod ◽  
Rebecca Jeanmonod
Keyword(s):  
United States ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Inflammatory Disease ◽  
Cranial Nerve ◽  
Cranial Nerves ◽  
The United States ◽  
Vector Borne Disease ◽  
Vector Borne ◽  
Multiple Cranial Nerve

Lyme disease is a tick-transmitted multisystem inflammatory disease caused by the spirocheteBorrelia burgdorferi. With more than 25,000 CDC reported cases annually, it has become the most common vector-borne disease in the United States. We report a case of 38-year-old man with Lyme disease presenting with simultaneous palsy of 3rd, 5th, 7th, 9th, and 10th cranial nerves.

scholarly journals Misdiagnosis of Lyme Disease With Unnecessary Antimicrobial Treatment Characterizes Patients Referred to an Academic Infectious Diseases Clinic

2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Takaaki Kobayashi ◽  
Yvonne Higgins ◽  
Roger Samuels ◽  
Aurasch Moaven ◽  
Abanti Sanyal ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Infectious Diseases ◽  
The United States ◽  
Antimicrobial Treatment ◽  
Community Settings ◽  
Academic Center ◽  
History Of ◽  
Observational Cohort ◽  
Vector Borne ◽  
Retrospective Observational Cohort Study

Abstract Background Although Lyme disease is the most common vector-borne infection in the United States, diagnostic accuracy within community settings is not well characterized. Methods A retrospective observational cohort study of patients referred to an academic center with a presumed diagnosis or concern for Lyme disease between 2000 and 2013 was performed to analyze diagnoses and treatments. Characteristics of those with Lyme disease and those misdiagnosed as having Lyme disease were compared. Results Of 1261 patients, 911 (72.2%) did not have Lyme disease, 184 (14.6%) had active or recent Lyme disease, 150 (11.9%) had a remote history of Lyme disease, and 16 (1.3%) were identified as having possible Lyme disease. Patients without current Lyme disease were more likely to be female (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.08–2.45), to have had symptoms for >3 months (OR, 8.78; 95% CI, 5.87–13.1), to have higher symptom counts (OR per additional symptom, 1.08; 95% CI, 1.02–1.13), to have had more Lyme-related laboratory testing (OR per additional laboratory test, 1.17; 95% CI, 1.03–1.32), and to have been diagnosed with what were regarded as coinfections (OR, 3.13; 95% CI, 1.14–8.57). Of the 911 patients without Lyme disease, 764 (83.9%) had received antimicrobials to treat Lyme disease or their coinfections. The percentage of patients established to have Lyme disease was lower than in earlier studies of referred populations. Conclusions Among patients referred to an academic Infectious Diseases practice for Lyme disease, incorrect diagnoses and unnecessary antibiotic treatment were common, both for Lyme disease and for coinfections.

scholarly journals Context matters: Contrasting behavioral and residential risk factors for Lyme disease between two high-incidence regions in the Northeastern and Midwestern U.S

2020 ◽  
Author(s):  
Gebbiena M. Bron ◽  
Maria del P. Fernandez ◽  
Scott R. Larson ◽  
Adam Maus ◽  
Dave Gustafson ◽  
...  
Keyword(s):  
United States ◽  
Risk Factors ◽  
Lyme Disease ◽  
Human Behavior ◽  
The United States ◽  
Protective Measure ◽  
Protective Measures ◽  
Outdoor Activities ◽  
High Incidence ◽  
Vector Borne

AbstractThe dynamics of zoonotic vector-borne diseases are determined by a complex set of parameters including human behavior that may vary with socio-ecological contexts. Lyme disease is the most common vector-borne disease in the United States and the Northeast and upper Midwest are the regions most affected - two areas with differing levels of urbanization and sociocultural settings. The probability of being diagnosed with Lyme disease is related to the risk of encounters with an infected blacklegged tick, which reflects both the environmental tick hazard and human behaviors. Herein, we compare behavioral and peridomestic risk factors associated with human-tick encounters between high-incidence states in the Northeast (New York and New Jersey) and Midwest (Wisconsin) of the United States. We used a smartphone application, The Tick App, as a novel survey tool, during spring and summer of 2018. Adaptive human behavior was identified in the relationship between outdoor activities and the use of preventive methods. More frequent recreational outdoor activities and gardening (a peridomestic activity) were associated with an increased likelihood of using personal protective measures. Weekly participation in non-seasonal recreational and peridomestic outdoor activities in spring and summer was associated with an increased likelihood of finding a tick in the fall or winter. Most outdoor activities were more frequently reported by participants from the Midwest than the Northeast. Participants in the Northeast reported less use of personal protective measures, but they reported more interventions to reduce the presence of peridomestic deer and ticks (i.e. pesticide applications on their property) than participants in the Midwest. Participants from the Midwest were more likely to kill rodents on their property. Context mattered, and our study illustrates the need for the assessment of personal behavior and tick exposure in these two Lyme disease-endemic regions to aid in targeted public health messaging to reduce tick-borne diseases.Highlights-Use of personal tick prevention was associated with more frequent outdoor activity-Personal protective measure use was higher in the Midwest than Northeast-Interventions reducing peridomestic deer and ticks more common in the Northeast

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