Effect of Dapsone Alone and in Combination with Intracellular Antibiotics Against the Biofilm Form of B. Burgdorferi

Overview

Journal BMC Res Notes

Publisher Biomed Central

Specialties Biology
General Medicine

Date 2020 Sep 30

PMID 32993780

Citations 8

Authors

Richard I Horowitz

Krithika Murali

Gauri Gaur

Phyllis R Freeman

Eva Sapi

Affiliations

Soon will be listed here.

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.

Citing Articles

Combining Double-Dose and High-Dose Pulsed Dapsone Combination Therapy for Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome and Co-Infections, Including Bartonella: A Report of 3 Cases and a Literature Review.

Horowitz R, Fallon J, Freeman P Microorganisms. 2024; 12(5).

PMID: 38792737 PMC: 11124288. DOI: 10.3390/microorganisms12050909.

Concurrent Infection of the Human Brain with Multiple Species.

Golovchenko M, Opelka J, Vancova M, Sehadova H, Kralikova V, Dobias M Int J Mol Sci. 2023; 24(23).

PMID: 38069228 PMC: 10707132. DOI: 10.3390/ijms242316906.

Comparison of the Efficacy of Longer versus Shorter Pulsed High Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome with Bartonellosis and Associated Coinfections.

Horowitz R, Fallon J, Freeman P Microorganisms. 2023; 11(9).

PMID: 37764145 PMC: 10537894. DOI: 10.3390/microorganisms11092301.

The Use of Natural Bioactive Nutraceuticals in the Management of Tick-Borne Illnesses.

Shor S, Schweig S Microorganisms. 2023; 11(7).

PMID: 37512931 PMC: 10384908. DOI: 10.3390/microorganisms11071759.

Lyme disease and the pursuit of a clinical cure.

Adkison H, Embers M Front Med (Lausanne). 2023; 10:1183344.

PMID: 37293310 PMC: 10244525. DOI: 10.3389/fmed.2023.1183344.

References

Feng J, Li T, Yee R, Yuan Y, Bai C, Cai M . Stationary phase persister/biofilm microcolony of Borrelia burgdorferi causes more severe disease in a mouse model of Lyme arthritis: implications for understanding persistence, Post-treatment Lyme Disease Syndrome (PTLDS), and treatment failure. Discov Med. 2019; 27(148):125-138. View

Jutras B, Lochhead R, Kloos Z, Biboy J, Strle K, Booth C . peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proc Natl Acad Sci U S A. 2019; 116(27):13498-13507. PMC: 6613144. DOI: 10.1073/pnas.1904170116. View

Feder Jr H, Abeles M, Bernstein M, Whitaker-Worth D, Grant-Kels J . Diagnosis, treatment, and prognosis of erythema migrans and Lyme arthritis. Clin Dermatol. 2006; 24(6):509-20. DOI: 10.1016/j.clindermatol.2006.07.012. View

Feng J, Wang T, Shi W, Zhang S, Sullivan D, Auwaerter P . Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library. Emerg Microbes Infect. 2015; 3(7):e49. PMC: 4126181. DOI: 10.1038/emi.2014.53. View

Sapi E, Balasubramanian K, Poruri A, Maghsoudlou J, Socarras K, Timmaraju A . Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas. Eur J Microbiol Immunol (Bp). 2016; 6(1):9-24. PMC: 4838982. DOI: 10.1556/1886.2015.00049. View

MacDonald A . Spirochetal cyst forms in neurodegenerative disorders,...hiding in plain sight. Med Hypotheses. 2006; 67(4):819-32. DOI: 10.1016/j.mehy.2006.04.025. View

Feng J, Zhang S, Shi W, Zhang Y . Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro. Antibiotics (Basel). 2017; 6(1). PMC: 5372990. DOI: 10.3390/antibiotics6010010. View

Feng J, Auwaerter P, Zhang Y . Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline. PLoS One. 2015; 10(3):e0117207. PMC: 4373819. DOI: 10.1371/journal.pone.0117207. View

Klempner M, Hu L, Evans J, Schmid C, JOHNSON G, Trevino R . Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001; 345(2):85-92. DOI: 10.1056/NEJM200107123450202. View

10.

Wormser G, Nadelman R, Dattwyler R, Dennis D, Shapiro E, Steere A . Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin Infect Dis. 2000; 31 Suppl 1:1-14. DOI: 10.1086/314053. View

11.

Donta S . Macrolide therapy of chronic Lyme Disease. Med Sci Monit. 2003; 9(11):PI136-42. View

12.

Feng J, Shi W, Zhang S, Zhang Y . Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from the NCI compound collection. Emerg Microbes Infect. 2016; 4:e31. PMC: 5176177. DOI: 10.1038/emi.2015.31. View

13.

Steere A, Angelis S . Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis. Arthritis Rheum. 2006; 54(10):3079-86. DOI: 10.1002/art.22131. View

14.

Garnham J, Taylor T, Turner P, Chasseaud L . Serum concentrations and bioavailability of rifampicin and isoniazid in combination. Br J Clin Pharmacol. 1976; 3(5):897-902. PMC: 1428926. DOI: 10.1111/j.1365-2125.1976.tb00644.x. View

15.

Miklossy J, Kasas S, Zurn A, McCall S, Yu S, McGeer P . Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis. J Neuroinflammation. 2008; 5:40. PMC: 2564911. DOI: 10.1186/1742-2094-5-40. View

16.

Sapi E, Bastian S, Mpoy C, Scott S, Rattelle A, Pabbati N . Characterization of biofilm formation by Borrelia burgdorferi in vitro. PLoS One. 2012; 7(10):e48277. PMC: 3480481. DOI: 10.1371/journal.pone.0048277. View

17.

Eppes S, Childs J . Comparative study of cefuroxime axetil versus amoxicillin in children with early Lyme disease. Pediatrics. 2002; 109(6):1173-7. DOI: 10.1542/peds.109.6.1173. View

18.

Brorson O, Brorson S . Transformation of cystic forms of Borrelia burgdorferi to normal, mobile spirochetes. Infection. 1997; 25(4):240-6. DOI: 10.1007/BF01713153. View

19.

Sapi E, Kasliwala R, Ismail H, Torres J, Oldakowski M, Markland S . The Long-Term Persistence of Antigens and DNA in the Tissues of a Patient with Lyme Disease. Antibiotics (Basel). 2019; 8(4). PMC: 6963883. DOI: 10.3390/antibiotics8040183. View

20.

Rudenko N, Golovchenko M, Kybicova K, Vancova M . Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters. Parasit Vectors. 2019; 12(1):237. PMC: 6521364. DOI: 10.1186/s13071-019-3495-7. View