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Antimicrobial Agents and Chemotherapy, October 1998, p. 2590-2594, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Characterization of Mutations in the rpoB Gene That Confer Rifampin Resistance in Staphylococcus aureus

Hélène Aubry-Damon,1,2 Claude-James Soussy,2 and Patrice Courvalin1,*

Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15,1 and Service de Bactériologie-Virologie-Hygiène, Hôpital Henri Mondor, 94010 Créteil,2 France

Received 9 March 1998/Returned for modification 10 June 1998/Accepted 8 July 1998

Mutations in the rifampin resistance-determining (Rif) regions of the rpoB gene of Staphylococcus aureus mutants obtained during therapy or in vitro were analyzed by gene amplification and sequencing. Each of the resistant clinical isolates, including five nonrelated clones and two strains isolated from the same patient, and of the 10 in vitro mutants had a single base pair change that resulted in an amino acid substitution in the beta  subunit of RNA polymerase. Eight mutational changes at seven positions were found in cluster I of the central Rif region. Certain substitutions (His481/Tyr and Asp471/Tyr [S. aureus coordinates]) were present in several mutants. Substitutions Gln468/Arg, His481/Tyr, and Arg484/His, which conferred high-level rifampin resistance, were identical or in the same codon as those described in other bacterial genera, whereas Asp550/Gly has not been reported previously. Substitutions at codon 477 conferred high- or low-level resistance, depending on the nature of the new amino acid. The levels of resistance of in vivo and one-step in vitro mutants carrying identical mutations were similar, suggesting that no other resistance mechanism was present in the clinical isolates. On the basis of these data and the population distribution of more than 4,000 clinical S. aureus isolates, we propose <= 0.5 and >= 8 µg/ml as new breakpoints for the clinical categorization of this species relative to rifampin.

* Corresponding author. Mailing address: Unité des Agents Antibactériens, Institut Pasteur, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: (33) (1) 45 68 83 20. Fax: (33) (1) 45 68 83 19. E-mail: pcourval{at}pasteur.fr.

Antimicrobial Agents and Chemotherapy, October 1998, p. 2590-2594, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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