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Antibiotics
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Pathogen–Host Interaction by Borrelia burgdorferi
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Pathogen–Host Interaction by Borrelia burgdorferi

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 43316

Special Issue Editor

Prof. Dr. Eva Sapi

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Borrelia burgdorferi senso lato (s.l.), the etiological agent of Lyme disease, is well known to disseminate to and colonize various organisms and tissues of its natural reservoir hosts, which are crucial steps for its pathogenicity and overall survival. To invade and persist in the different tissues, B. burgdorferi s.l. has developed several very sophisticated strategies, including manipulating innate and adaptive immune systems, binding to host proteins to initiate vascular and extracellular matrix interactions, and even highjacking and stimulating host proteases to digest and remodel healthy tissues. Furthermore, intracellular localization of B. burgdorferi s.l. is also reported for different eukaryotic cells that can further help to evade the immune system and other environmental stress factors.

A clear understanding of the exact mechanism of host dissemination and invasion by B. burgdorferi s.l could help us develop therapeutic targets for chronic conditions such as Lyme carditis, arthritis, and neuroborreliosis.

This Special Issue seeks manuscript submissions that further our understanding of B. burgdorferi s.l. host dissemination and tissue invasion though original research articles, short communications, reviews, case reports, and perspectives.

Prof. Dr. Eva Sapi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Lyme disease
  • spirochetes
  • infection
  • biofilm
  • persisters
  • antibiotic resistance
  • pathogen-host interaction

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Published Papers (3 papers)

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Research

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18 pages, 5137 KiB  
Article
Ex Vivo Murine Skin Model for B. burgdorferi Biofilm
by Jason P. Torres, Alireza G. Senejani, Gauri Gaur, Michael Oldakowski, Krithika Murali and Eva Sapi
Antibiotics 2020, 9(9), 528; https://doi.org/10.3390/antibiotics9090528 - 19 Aug 2020
Cited by 8 | Viewed by 4319
Abstract
Borrelia burgdorferi, the causative agent of Lyme disease, has been recently shown to form biofilm structures in vitro and in vivo. Biofilms are tightly clustered microbes characterized as resistant aggregations that allow bacteria to withstand harsh environmental conditions, including the administration [...] Read more.
Borrelia burgdorferi, the causative agent of Lyme disease, has been recently shown to form biofilm structures in vitro and in vivo. Biofilms are tightly clustered microbes characterized as resistant aggregations that allow bacteria to withstand harsh environmental conditions, including the administration of antibiotics. Novel antibiotic combinations have recently been identified for B. burgdorferi in vitro, however, due to prohibiting costs, those agents have not been tested in an environment that can mimic the host tissue. Therefore, researchers cannot evaluate their true effectiveness against B. burgdorferi, especially its biofilm form. A skin ex vivo model system could be ideal for these types of experiments due to its cost effectiveness, reproducibility, and ability to investigate host–microbial interactions. Therefore, the main goal of this study was the establishment of a novel ex vivo murine skin biopsy model for B. burgdorferi biofilm research. Murine skin biopsies were inoculated with B. burgdorferi at various concentrations and cultured in different culture media. Two weeks post-infection, murine skin biopsies were analyzed utilizing immunohistochemical (IHC), reverse transcription PCR (RT-PCR), and various microscopy methods to determine B. burgdorferi presence and forms adopted as well as whether it remained live in the skin tissue explants. Our results showed that murine skin biopsies inoculated with 1 × 107 cells of B. burgdorferi and cultured in BSK-H + 6% rabbit serum media for two weeks yielded not just significant amounts of live B. burgdorferi spirochetes but biofilm forms as well. IHC combined with confocal and atomic force microscopy techniques identified specific biofilm markers and spatial distribution of B. burgdorferi aggregates in the infected skin tissues, confirming that they are indeed biofilms. In the future, this ex vivo skin model can be used to study development and antibiotic susceptibility of B. burgdorferi biofilms in efforts to treat Lyme disease effectively. Full article
(This article belongs to the Special Issue Pathogen–Host Interaction by Borrelia burgdorferi)
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15 pages, 2678 KiB  
Article
Effect of Borrelia burgdorferi Outer Membrane Vesicles on Host Oxidative Stress Response
by Keith Wawrzeniak, Gauri Gaur, Eva Sapi and Alireza G. Senejani
Antibiotics 2020, 9(5), 275; https://doi.org/10.3390/antibiotics9050275 - 25 May 2020
Cited by 16 | Viewed by 4192
Abstract
Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including Borrelia burgdorferi, the causative agent of Lyme disease. The functional relationship between B. burgdorferi OMVs and host neuron homeostasis is not well understood. [...] Read more.
Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including Borrelia burgdorferi, the causative agent of Lyme disease. The functional relationship between B. burgdorferi OMVs and host neuron homeostasis is not well understood. The objective of this study was to examine how B. burgdorferi OMVs impact the host cell environment. First, an in vitro model was established by co-culturing human BE2C neuroblastoma cells with B. burgdorferi B31. B. burgdorferi was able to invade BE2C cells within 24 h. Despite internalization, BE2C cell viability and levels of apoptosis remained unchanged, but resulted in dramatically increased production of MCP-1 and MCP-2 cytokines. Elevated secretion of MCP-1 has previously been associated with changes in oxidative stress. BE2C cell mitochondrial superoxides were reduced as early as 30 min after exposure to B. burgdorferi and OMVs. To rule out whether BE2C cell antioxidant response is the cause of decline in superoxides, superoxide dismutase 2 (SOD2) gene expression was assessed. SOD2 expression was reduced upon exposure to B. burgdorferi, suggesting that B. burgdorferi might be responsible for superoxide reduction. These results suggest that B. burgdorferi modulates cell antioxidant defense and immune system reaction in response to the bacterial infection. In summary, these results show that B. burgdorferi OMVs serve to directly counter superoxide production in BE2C neurons, thereby ‘priming’ the host environment to support B. burgdorferi colonization. Full article
(This article belongs to the Special Issue Pathogen–Host Interaction by Borrelia burgdorferi)
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Other

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24 pages, 1130 KiB  
Case Report
Efficacy of Double-Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Retrospective Chart Review
by Richard I. Horowitz and Phyllis R. Freeman
Antibiotics 2020, 9(11), 725; https://doi.org/10.3390/antibiotics9110725 - 22 Oct 2020
Cited by 10 | Viewed by 34086
Abstract
Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double-dose dapsone combination therapy (DDD CT) for a total of 7–8 weeks. At the completion of therapy, all three patients’ major Lyme [...] Read more.
Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double-dose dapsone combination therapy (DDD CT) for a total of 7–8 weeks. At the completion of therapy, all three patients’ major Lyme symptoms remained in remission for a period of 25–30 months. A retrospective chart review of 37 additional patients undergoing DDD CT therapy (40 patients in total) was also performed, which demonstrated tick-borne symptom improvements in 98% of patients, with 45% remaining in remission for 1 year or longer. In conclusion, double-dose dapsone therapy could represent a novel and effective anti-infective strategy in chronic Lyme disease/post-treatment Lyme disease syndrome (PTLDS), especially in those individuals who have failed regular dose dapsone combination therapy (DDS CT) or standard antibiotic protocols. A randomized, blinded, placebo-controlled trial is warranted to evaluate the efficacy of DDD CT in those individuals with chronic Lyme disease/PTLDS. Full article
(This article belongs to the Special Issue Pathogen–Host Interaction by Borrelia burgdorferi)
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