Abstract

Background: Borrelia sp, which is a pathogenic agent of Lyme diseases in mammals, has become an increasing problem worldwide due to the emergence of persistence. In this study we investigated whether a defined composition of naturally occurring substances could display a broad and synergistic action in vitro against both active and persistent forms of Borrelia spp.Methods: A formulation of six plant-derived compounds combined at their 1/32-1/2 MIC values was tested in vitro against two species of Borrelia recognized as causative agents of Lyme disease in North America and Europe.Results: The results showed that a composition of baicalein, luteolin, rosmarinic acid, monolaurin, cis-2 decenoic acid, and iodine at their 1/8 MIC values has significant synergistic effect against the active and persisting latent forms. This composition revealed anti-oxidative properties affecting Borrelia’s membrane but not DNA. Finally, we observed its inhibitory effect on the release of IL-1α, IL-1β, and IL-6 by human CD14+ monocytes stimulated with live Borrelia sp.Conclusion: These results suggest that such a formulation of compounds might be considered and further explored for its significant pleotropic anti-Borreliae efficacy. Additional in vivo and human studies are warranted to validate this possibility.

Highlights

  • Lyme Disease (LD) is a multi-systemic bacterial infection that has become the most frequent vectorborne disease in North America and Europe, and it is a growing health concern worldwide [1]

  • Recent in vitro studies demonstrate that a triple combination of antibiotics such as doxycycline/ daptomycin/cefoperazone can be considered as an option since it showed to be effective against persistent forms of Borrelia burgdorferi [25]

  • We evaluated the anti-Borreliae effect of the defined composition of phytochemicals

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Summary

Introduction

Lyme Disease (LD) is a multi-systemic bacterial infection that has become the most frequent vectorborne disease in North America and Europe, and it is a growing health concern worldwide [1]. Granular structures) and bio film-like aggregates [4,5,6,7,8] The presence of these atypical forms has been demonstrated in vitro and in humans and is suggested as one of the possible factors that may attribute to the persistence of this illness [9,10,11,12,13]. The commonly prescribed drugs for LD patients are limited to a major pharmacological class of antibiotics belonging to beta lactams and tetracycline’s, and include doxycycline, amoxicillin, and cefuroxime axetil [1] Their single administration in vitro showed to be effective against the active form of Borrelia sp. Recent in vitro studies demonstrate that a triple combination of antibiotics such as doxycycline/ daptomycin/cefoperazone can be considered as an option since it showed to be effective against persistent forms of Borrelia burgdorferi [25]. Additional in vivo and human studies are warranted to validate this possibility

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