Effect of rpoB mutations conferring rifampin resistance on fitness of Mycobacterium tuberculosis
2004 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 48, no 4, 1289-1294 p.Article in journal (Refereed) Published
Rifampin is a major drug used in the treatment of tuberculosisinfections, and increasing rifampin resistance represents aworldwide clinical problem. Resistance to rifampin is causedby mutations in the rpoB gene, encoding the ß-subunitof RNA polymerase. We examined the effect of three differentrpoB mutations on the fitness of Mycobacterium tuberculosis.Rifampin-resistant mutants were isolated from a virulent clinicalisolate of M. tuberculosis (strain Harlingen) in vitro at amutation frequency of 2.3 x 10-8. Mutations in the rpoB genewere identified, and the growth rates of three defined mutantswere measured by competition with the susceptible parent strainin laboratory medium and by single cultures in a macrophagecell line and in laboratory medium. All of the mutants showeda decreased growth rate in the three assays. The relative fitnessof the mutants varied between 0.29 and 0.96 (that of the susceptiblestrain was set to 1.0) depending on the specific mutant andassay system. Unexpectedly, the relative fitness ranking ofthe mutants differed between the different assays. In conclusion,rifampin resistance is associated with a cost that is conditional.
Place, publisher, year, edition, pages
2004. Vol. 48, no 4, 1289-1294 p.
IdentifiersURN: urn:nbn:se:uu:diva-68008PubMedID: 15047531OAI: oai:DiVA.org:uu-68008DiVA: diva2:95919