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Special Issue "Antibiotics Resistance of Borrelia"

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 109441

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Special Issue Editor

Prof. Dr. Eva Sapi

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Guest Editor

Department of Biology and Environment Science, University of New Haven, West Haven, CT 06516, USA
Interests: Lyme disease; spirochetes; infection; biofilm; persisters; antibiotic resistance; connection of cancer to bacterial infections
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Special Issue Information

Dear Colleagues,

Over the years, the severity of infectious diseases and the inability to effectively treat them using antibiotics has become a rapidly growing epidemic. Lyme disease, which is caused by the spirochete Borrelia, is one of the fastest growing tick-borne multisystemic diseases, with 300,000 reported cases/year just in the United States. While administering antibiotics can be effective for some patients, relapse often occurs when the treatment is discontinued. The reason for relapse remains unknown, but there are recent studies suggesting the presence of “pesisters cells” and biofilm forms with surprisingly high resistance to the antimicrobials currently used to treat Lyme disease. Therefore, there is a pressing need to better understand how these defensive forms can evade our therapeutic treatments with the ultimate goal of finding effective anti-microbials to treat all forms of Borrelia. In this Special Issue on the “Antibiotics Resistance of Borrelia” we will highlight the latest research exploring new strategies to combat Lyme disease.

Prof. Dr. Eva Sapi
Guest Editor

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Keywords

Microbiology
bacteriology
pathogens
Lyme disease
spirochetes
antibiotics
antimicrobials
resistance
persisters
biofilm
drug discovery

Published Papers (6 papers)

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Research

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Open AccessArticle

The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease

and

Antibiotics 2019, 8(4), 183; https://doi.org/10.3390/antibiotics8040183 - 11 Oct 2019

Cited by 24 | Viewed by 33448

Abstract

Whether Borrelia burgdorferi, the causative agent of Lyme disease, can persist for long periods in the human body has been a controversial question. The objective of this study was to see if we could find B. burgdorferi in a Lyme disease patient after a long clinical course and after long-term antibiotic treatment. Therefore, we investigated the potential presence of B. burgdorferi antigens and DNA in human autopsy tissues from a well-documented serum-, PCR-, and culture-positive Lyme disease patient, a 53-year-old female from northern Westchester County in the lower Hudson Valley Region of New York State, who had received extensive antibiotic treatments during extensive antibiotic treatments over the course of her 16-year-long illness. We also asked what form the organism might take, with special interest in the recently found antibiotic-resistant aggregate form, biofilm. We also examined the host tissues for the presence of inflammatory markers such as CD3+ T lymphocytes. Autopsy tissue sections of the brain, heart, kidney, and liver were analyzed by histological and immunohistochemical methods (IHC), confocal microscopy, fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR), and whole-genome sequencing (WGS)/metagenomics. We found significant pathological changes, including borrelial spirochetal clusters, in all of the organs using IHC combined with confocal microscopy. The aggregates contained a well-established biofilm marker, alginate, on their surfaces, suggesting they are true biofilm. We found B. burgdorferi DNA by FISH, polymerase chain reaction (PCR), and an independent verification by WGS/metagenomics, which resulted in the detection of B. burgdorferi sensu stricto specific DNA sequences. IHC analyses showed significant numbers of infiltrating CD3+ T lymphocytes present next to B. burgdorferi biofilms. In summary, we provide several lines of evidence that suggest that B. burgdorferi can persist in the human body, not only in the spirochetal but also in the antibiotic-resistant biofilm form, even after long-term antibiotic treatment. The presence of infiltrating lymphocytes in the vicinity of B. burgdorferi biofilms suggests that the organism in biofilm form might trigger chronic inflammation. Full article

(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)

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Open AccessArticle

Cytokine Expression Patterns and Single Nucleotide Polymorphisms (SNPs) in Patients with Chronic Borreliosis

by Tabea M. Hein,

and

Antibiotics 2019, 8(3), 107; https://doi.org/10.3390/antibiotics8030107 - 30 Jul 2019

Cited by 5 | Viewed by 3694

Abstract

(1) Background: Genetically based hyperinflammation may play a role in pathogen defense. We here questioned whether alterations in circulating monocytes/macrophages, inflammatory biomarkers and a functional SNP (single nucleotide polymorphisms) of the Interleukin-6 (IL-6) promotor might play a role in patients with persistent, and treatment resistant borreliosis. (2) Methods: Leukocyte subpopulations were studied by flow cytometry; plasma cytokines were determined by a chemiluminescence based ELISA (Immulite^®), and genotypes of the IL-6 promotor SNP rs1800795 were determined by pyrosequencing. (3) Results: In a cohort of n = 107 Lyme borreliosis patients, who concomitantly manifested either malignant diseases (group 1), autoimmune disorders (group 2), neurological diseases (group 3), or morbidities caused by multiple other infectious complications (group 4), we found decreased numbers of anti-inflammatory CD163-positive macrophages, elevated concentrations of inflammatory cytokines, and an imbalance of IL-6 promotor SNP rs1800795 genotypes. The most prominently upregulated cytokines were IL-1β, and IL-8. (4) Conclusions: Increased pro-inflammatory phenotypes identified by monocyte/macrophage subtypes and concomitantly increased cytokines appear to be valid to monitor disease activity in patients with persistent Lyme borreliosis. Patterns may vary by additional co-morbidities. In patients with autoimmune diseases, increased frequencies of a heterozygous IL-6 promotor SNP rs1800795 were identified. This functional SNP may guide chronic inflammation, impacting other cytokines to trigger trigger chronicity and therapeutic resistance in Lyme borreliosis. Full article

(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)

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Open AccessArticle

Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases

Kenneth B. Liegner

Antibiotics 2019, 8(2), 72; https://doi.org/10.3390/antibiotics8020072 - 30 May 2019

Cited by 21 | Viewed by 36295

Abstract

Three patients, each of whom had required intensive open-ended antimicrobial therapy for control of the symptoms of chronic relapsing neurological Lyme disease and relapsing babesiosis, were able to discontinue treatment and remain clinically well for periods of observation of 6–23 months following the completion of a finite course of treatment solely with disulfiram. One patient relapsed at six months and is being re-treated with disulfiram. Full article

(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)

Review

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Open AccessReview

Complement Evasion in Borrelia spirochetes: Mechanisms and Opportunities for Intervention

Jonathan W. Locke

Antibiotics 2019, 8(2), 80; https://doi.org/10.3390/antibiotics8020080 - 13 Jun 2019

Cited by 8 | Viewed by 6819

Abstract

Lyme disease (LD) is an increasingly prevalent, climate change-accelerated, vector-borne infectious disease with significant morbidity and cost in a proportion of patients who experience ongoing symptoms after antibiotic treatment, a condition known as post-treatment Lyme disease syndrome (PTLDS). Spirochetal bacteria of Borrelia species are the causative agents of LD. These obligate parasites have evolved sophisticated immune evasion mechanisms, including the ability to defeat the innate immune system’s complement cascade. Research on complement function and Borrelia evasion mechanisms, focusing on human disease, is reviewed, highlighting opportunities to build on existing knowledge. Implications for the development of new antibiotic therapies having the potential to prevent or cure PTLDS are discussed. It is noted that a therapy enabling the complement system to effectively counter Borrelia might have lower cost and fewer side-effects and risks than broad-spectrum antibiotic use and could avert the need to develop and administer a vaccine. Full article

(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)

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Other

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Open AccessConcept Paper

Chronic Lyme Disease: An Evidence-Based Definition by the ILADS Working Group

Joseph Jr. Burrascano, Jr.

Robert Bransfield

and

Elizabeth L. Maloney

Antibiotics 2019, 8(4), 269; https://doi.org/10.3390/antibiotics8040269 - 16 Dec 2019

Cited by 15 | Viewed by 20912

Abstract

Objective: Chronic Lyme disease has been a poorly defined term and often dismissed as a fictitious entity. In this paper, the International Lyme and Associated Diseases Society (ILADS) provides its evidence-based definition of chronic Lyme disease. Definition: ILADS defines chronic Lyme disease (CLD) as a multisystem illness with a wide range of symptoms and/or signs that are either continuously or intermittently present for a minimum of six months. The illness is the result of an active and ongoing infection by any of several pathogenic members of the Borrelia burgdorferi sensu lato complex (Bbsl). The infection has variable latency periods and signs and symptoms may wax, wane and migrate. CLD has two subcategories, CLD, untreated (CLD-U) and CLD, previously treated (CLD-PT). The latter requires that CLD manifestations persist or recur following treatment and are present continuously or in a relapsing/remitting pattern for a duration of six months or more. Methods: Systematic review of over 250 peer reviewed papers in the international literature to characterize the clinical spectrum of CLD-U and CLD-PT. Conclusion: This evidence-based definition of chronic Lyme disease clarifies the term’s meaning and the literature review validates that chronic and ongoing Bbsl infections can result in chronic disease. Use of this CLD definition will promote a better understanding of the infection and facilitate future research of this infection. Full article

(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)

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Open AccessCase Report

Potential Persistent Borrelia Infection and Response to Antibiotic Therapy; a Clinical Case Study and Review of Recent Literature

Cozette Moysa

Ross Murtagh

and

John S. Lambert

Antibiotics 2019, 8(4), 223; https://doi.org/10.3390/antibiotics8040223 - 14 Nov 2019

Cited by 3 | Viewed by 6576

Abstract

This report describes the case of an individual who was clinically diagnosed with Lyme borreliosis and initially responded to standard antibiotic therapy. Subsequent to treatment cessation, the patient experienced symptomatic rebound and failed to respond to a second course of the same antibiotic. The patient was eventually diagnosed with both Borrelia and Anaplasma infections by serological testing performed in a private laboratory. Following a two-month course of combination antibiotic therapy, the patient responded clinically, with a return to almost normal functioning. We discuss this case in the context of recent pre-clinical research examining potential Borrelial persistence despite antibiotic therapy. Full article

(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)

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