Genetic Bases of the Rifampin Resistance Phenotype inBrucellaspp

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Abstract
Rifampin is one of the most potent and broad-spectrum antibiotics against bacterial pathogens. Its bactericidal activity is due to its ability to bind to the β subunit of the DNA-dependent RNA polymerase encoded by therpoBgene. Mutations of therpoBgene have been characterized in rifampin-resistant (Rifr) strains ofEscherichia coliandMycobacterium tuberculosis.The genetic bases of RifrinBrucellaspp. are still unknown. In the present study, the nucleotide sequences of therpoBgene of the Rifrvaccine strainBrucella abortusRB51 and of 20 Rifrclones derived in our laboratory from twoBrucella melitensisisolates were determined. These sequences were then compared to those of the respective rifampin-susceptible (Rifs) parental strains and to the publishedB. melitensisstrain 16M. All Rifrstrains carried one or more missense mutations mapping in two regions of therpoBgene. These two “hot” regions were investigated in eight additional RifrBrucellalaboratory mutants and in 20 reference RifsBrucellastrains.rpoBmutations were found in all Rifrmutants. In contrast, no missense mutations were found in any analyzed Rifsstrains. Our results represent the first from a study of the molecular characterization ofrpoBmutations in resistantBrucellastrains and provide an additional proof of the association of specificrpoBmutations with the development of the Rifrphenotype in prokaryotes. In addition, because of the relationship between Rifrand the attenuation of virulence inBrucellaspp., studies of virulence in these mutants may provide useful information about the genetic basis of pathogenesis inBrucella.