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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
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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