Isolation of three Mycobacterium ulcerans strains resistant to rifampin after experimental chemotherapy of mice.
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 micro g/ml. Three mutants were isolated after rifampin monotherapy. Two were resistant to rifampin at 8 micro g/ml, and one was resistant to rifampin at 32 micro g/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.
Marsollier
Laurent
L
Laboratoire de Bactériologie-Virologie-Hygiène Hospitalière, CHU, 49033 Angers Cedex 01, France. laurentmarsollier@hotmail.com
Honoré
Nadine
N
Legras
Pierre
P
Manceau
Anne Lise
AL
Kouakou
Henri
H
Carbonnelle
Bernard
B
Cole
Stewart T
ST
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy* / Q000473:pathology; D019911:Mycobacterium ulcerans / Q000187:drug effects* / Q000235:genetics; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use*
D000904:Antibiotics, Antitubercular; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin