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Targeting the Mycobacterium ulcerans cytochrome bc1:aa3 for the treatment of Buruli ulcer

Scherr, Nicole and Bieri, Raphael and Thomas, Sangeeta S. and Chauffour, Aurélie and Kalia, Nitin Pal and Schneide, Paul and Ruf, Marie-Thérèse and Lamelas, Araceli and Manimekalai, Malathy S. S. and Grüber, Gerhard and Ishii, Norihisa and Suzuki, Koichi and Tanner, Marcel and Moraski, Garrett C. and Miller, Marvin J. and Witschel, Matthias and Jarlier, Vincent and Pluschke, Gerd and Pethe, Kevin. (2018) Targeting the Mycobacterium ulcerans cytochrome bc1:aa3 for the treatment of Buruli ulcer. Nature Communications, 9. p. 5370.

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Abstract

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical skin disease that is most commonly found in children from West and Central Africa. Despite the severity of the infection, therapeutic options are limited to antibiotics with severe side effects. Here, we show that M. ulcerans is susceptible to the anti-tubercular drug Q203 and related compounds targeting the respiratory cytochrome bc; 1; :aa; 3; . While the cytochrome bc; 1; :aa; 3; is the primary terminal oxidase in Mycobacterium tuberculosis, the presence of an alternate bd-type terminal oxidase limits the bactericidal and sterilizing potency of Q203 against this bacterium. M. ulcerans strains found in Buruli ulcer patients from Africa and Australia lost all alternate terminal electron acceptors and rely exclusively on the cytochrome bc; 1; :aa; 3; to respire. As a result, Q203 is bactericidal at low dose against M. ulcerans replicating in vitro and in mice, making the drug a promising candidate for Buruli ulcer treatment.
Faculties and Departments:03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Malaria Vaccines (Tanner)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Interventions > Malaria Vaccines (Tanner)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Molecular Immunology (Pluschke)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Medicine > Diagnostic (Marti)
UniBasel Contributors:Scherr, Nicole and Bieri, Raphael and Ruf, Marie-Therese and Lamelas Cabello, Araceli and Tanner, Marcel and Pluschke, Gerd
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:15 Jan 2019 14:15
Deposited On:15 Jan 2019 14:15

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