Effect of dapsone alone and in combination with intracellular antibiotics against the biofilm form of B. burgdorferi
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BMC Research Notes Open Access
RESEARCH NOTE
Effect of dapsone alone and in combination with intracellular antibiotics against the biofilm form of B. burgdorferi Richard I. Horowitz1,2* , Krithika Murali3, Gauri Gaur3, Phyllis R. Freeman2 and Eva Sapi3
Abstract Objective: Lyme disease is a tick-borne, multisystemic disease caused by Borrelia burgdorferi. Standard treatments for early Lyme disease include short courses of oral antibiotics but relapses often occur after discontinuation of treatment. Several studies have suggested that ongoing symptoms may be due to a highly antibiotic resistant form of B. burgdorferi called biofilms. Our recent clinical study reported the successful use of an intracellular mycobacterium persister drug used in treating leprosy, diaminodiphenyl sulfone (dapsone), in combination therapy for the treatment of Lyme disease. In this in vitro study, we evaluated the effectiveness of dapsone individually and in combination with cefuroxime and/or other antibiotics with intracellular activity including doxycycline, rifampin, and azithromycin against Borrelia biofilm forms utilizing crystal violet biofilm mass, and dimethyl methylene blue glycosaminoglycan assays combined with Live/Dead fluorescent microscopy analyses. Results: Dapsone, alone or in various combinations with doxycycline, rifampin and azithromycin produced a significant reduction in the mass and protective glycosaminoglycan layer and overall viability of B. burgdorferi biofilm forms. This in vitro study strongly suggests that dapsone combination therapy could represent a novel and effective treatment option against the biofilm form of B. burgdorferi. Keywords: Lyme disease, Borrelia burgdorferi, Biofilm, Dapsone Introduction Lyme disease is the number one vector-borne illness in the United States caused by B. burgdorferi species and transmitted via the bite of Ixodes ticks [1–3]. Successful frontline treatments for early Lyme disease involve using antibiotics including doxycycline, amoxicillin, cefuroxime axetil, and ceftriaxone [4–7]. Although standard antibiotic therapy is effective in most cases of early Lyme disease [5], CDC reports suggest that greater than 10–20% of Lyme patients who have been treated for an Erythema migrans (EM) rash, a classical early manifestation of Lyme disease, continue to experience symptoms *Correspondence: [email protected] 1 HHS Babesia and Tick-borne Pathogens Subcommittee, Washington, DC 20201, USA Full list of author information is available at the end of the article
of fatigue, musculoskeletal pain, and cognitive impairment despite appropriate treatment [8–13]. Several theories to explain persistent symptoms have been suggested, including immune evasion in privileged sites [14], antigenic variation [15], persistent antigenic stimulation [16], biofilm formation [17, 18] and B. burgdorferi persister cells, a highly resistant bacterial form which may protect the bacteria from antibacterial therapy. B. burgdorferi can exist in spirochetal, round body forms, intracellularly, as well as in new
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