Isolation of Three Mycobacterium ulcerans Strains Resistant to Rifampin after Experimental Chemotherapy of Mice

Author:

Marsollier Laurent1,Honoré Nadine2,Legras Pierre3,Manceau Anne Lise1,Kouakou Henri4,Carbonnelle Bernard1,Cole Stewart T.2

Affiliation:

1. Laboratoire de Bactériologie-Virologie-Hygiène Hospitalière, CHU, 49033 Angers Cedex 01

2. Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 75724 Paris Cedex 15

3. Animalerie Hospitalo-Universitaire, Faculté de Médecine, 49000 Angers, France

4. Institut Raoul Follereau, Adzopé, Côte d'Ivoire

Abstract

ABSTRACT By use of a murine model for Buruli ulcer, Mycobacterium ulcerans was found to be susceptible to rifampin, with the MIC being 0.5 to 1 μg/ml. Three mutants were isolated after rifampin monotherapy. Two were resistant to rifampin at 8 μg/ml, and one was resistant to rifampin at 32 μg/ml. The mutants harbored Ser416Phe mutations and His420Tyr mutations in the rpoB gene, and these mutations have also been found to be responsible for rifampin resistance in the leprosy and tubercle bacilli. The results indicate that while rifampin may be active against M. ulcerans , it should never be used as monotherapy in humans.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference27 articles.

1. Asiedu K. R. Sherpbier and M. C. Raviglione. 2000. Buruli ulcer Mycobacterium ulcerans infection. WHO Global Buruli Ulcer Initiative. Report 2000. World Health Organization Geneva Switzerland.

2. Canetti, G., N. Rist, and J. Grosset. 1963. Mesure de la sensibilité du bacille tuberculeux par la méthode des proportions. Méthodologie, critères de résistance, résultats, interprétations. Rev. Tuberc. Pneumol.27:217-272.

3. Darie, H., S. Djakeaux, and A. Cautoclaud. 1994. Therapeutic approach in Mycobacterium ulcerans infections. Bull. Soc. Pathol. Exot.87:19-21.

4. Activities of Several Antimicrobials against Mycobacterium ulcerans Infection in Mice

5. De Gentile, P. L., C. Mahaza, F. Rolland, B. Carbonnelle, J. L. Verret, and D. Chabasse. 1992. Cutaneous ulcer from Mycobacterium ulcerans. Apropos of 1 case in French Guyana. Bull. Soc. Pathol. Exot.85:212-214.

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