This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aubry-Damon, H.
Right arrow Articles by Courvalin, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aubry-Damon, H.
Right arrow Articles by Courvalin, P.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:

  • Luczak-Kadlubowska, A., Sulikowska, A., Empel, J., Piasecka, A., Orczykowska, M., Kozinska, A., Hryniewicz, W. (2008). Countrywide Molecular Survey of Methicillin-Resistant Staphylococcus aureus Strains in Poland. J. Clin. Microbiol. 46: 2930-2937 [Abstract] [Full Text]  
  • Mullin, S., Rothstein, D. M., Murphy, C. K. (2006). Activity of Novel Benzoxazinorifamycins against Rifamycin-Resistant Streptococcus pyogenes.. Antimicrob. Agents Chemother. 50: 1908-1909 [Full Text]  
  • Murphy, C. K., Mullin, S., Osburne, M. S., van Duzer, J., Siedlecki, J., Yu, X., Kerstein, K., Cynamon, M., Rothstein, D. M. (2006). In Vitro Activity of Novel Rifamycins against Rifamycin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 50: 827-834 [Abstract] [Full Text]  
  • O'Neill, A. J., Huovinen, T., Fishwick, C. W. G., Chopra, I. (2006). Molecular Genetic and Structural Modeling Studies of Staphylococcus aureus RNA Polymerase and the Fitness of Rifampin Resistance Genotypes in Relation to Clinical Prevalence. Antimicrob. Agents Chemother. 50: 298-309 [Abstract] [Full Text]  
  • Ferrandiz, M. J., Ardanuy, C., Linares, J., Garcia-Arenzana, J. M., Cercenado, E., Fleites, A., de la Campa, A. G., the Spanish Pneumococcal Infection Study Network, (2005). New Mutations and Horizontal Transfer of rpoB among Rifampin-Resistant Streptococcus pneumoniae from Four Spanish Hospitals. Antimicrob. Agents Chemother. 49: 2237-2245 [Abstract] [Full Text]  
  • Trong, H. N., Prunier, A.-L., Leclercq, R. (2005). Hypermutable and Fluoroquinolone-Resistant Clinical Isolates of Staphylococcus aureus. Antimicrob. Agents Chemother. 49: 2098-2101 [Abstract] [Full Text]  
  • Kawamura, N., Kurokawa, K., Ito, T., Hamamoto, H., Koyama, H., Kaito, C., Sekimizu, K. (2005). Participation of Rho-dependent transcription termination in oxidative stress sensitivity caused by an rpoB mutation. GENES CELLS 10: 477-487 [Abstract] [Full Text]  
  • Xu, M., Zhou, Y. N., Goldstein, B. P., Jin, D. J. (2005). Cross-Resistance of Escherichia coli RNA Polymerases Conferring Rifampin Resistance to Different Antibiotics. J. Bacteriol. 187: 2783-2792 [Abstract] [Full Text]  
  • Yu, J., Wu, J., Francis, K. P., Purchio, T. F., Kadurugamuwa, J. L. (2005). Monitoring in vivo fitness of rifampicin-resistant Staphylococcus aureus mutants in a mouse biofilm infection model. J Antimicrob Chemother 55: 528-534 [Abstract] [Full Text]  
  • Kutlin, A., Kohlhoff, S., Roblin, P., Hammerschlag, M. R., Riska, P. (2005). Emergence of Resistance to Rifampin and Rifalazil in Chlamydophila pneumoniae and Chlamydia trachomatis. Antimicrob. Agents Chemother. 49: 903-907 [Abstract] [Full Text]  
  • Achour, W., Guenni, O., Fines, M., Leclercq, R., Ben Hassen, A. (2004). rpoB Mutations in Streptococcus mitis Clinical Isolates Resistant to Rifampin. Antimicrob. Agents Chemother. 48: 2757-2759 [Abstract] [Full Text]  
  • Enne, V. I., Delsol, A. A., Roe, J. M., Bennett, P. M. (2004). Rifampicin resistance and its fitness cost in Enterococcus faecium. J Antimicrob Chemother 53: 203-207 [Abstract] [Full Text]  
  • Kim, M., Wolff, E., Huang, T., Garibyan, L., Earl, A. M., Battista, J. R., Miller, J. H. (2004). Developing a Genetic System in Deinococcus radiodurans for Analyzing Mutations. Genetics 166: 661-668 [Abstract] [Full Text]  
  • Nolte, O., Muller, M., Reitz, S., Ledig, S., Ehrhard, I., Sonntag, H.-G. (2003). Description of new mutations in the rpoB gene in rifampicin-resistant Neisseria meningitidis selected in vitro in a stepwise manner. J Med Microbiol 52: 1077-1081 [Abstract] [Full Text]  
  • Dreses-Werringloer, U., Padubrin, I., Kohler, L., Hudson, A. P. (2003). Detection of Nucleotide Variability in rpoB in both Rifampin-Sensitive and Rifampin-Resistant Strains of Chlamydia trachomatis. Antimicrob. Agents Chemother. 47: 2316-2318 [Abstract] [Full Text]  
  • Meier, P. S., Utz, S., Aebi, S., Muhlemann, K. (2003). Low-Level Resistance to Rifampin in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 47: 863-868 [Abstract] [Full Text]  
  • Schaaff, F., Reipert, A., Bierbaum, G. (2002). An Elevated Mutation Frequency Favors Development of Vancomycin Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 46: 3540-3548 [Abstract] [Full Text]  
  • O'Neill, A. J., Chopra, I. (2002). Insertional inactivation of mutS in Staphylococcus aureus reveals potential for elevated mutation frequencies, although the prevalence of mutators in clinical isolates is low. J Antimicrob Chemother 50: 161-169 [Abstract] [Full Text]  
  • Nilius, A. M., Hensey-Rudloff, D. M., Reimann, M. A., Flamm, R. K. (2002). Comparison of selection for mutants with reduced susceptibility to ABT-773, erythromycin and rifampicin in respiratory tract pathogens. J Antimicrob Chemother 49: 831-836 [Abstract] [Full Text]  
  • Aubry-Damon, H., Galimand, M., Gerbaud, G., Courvalin, P. (2002). rpoB Mutation Conferring Rifampin Resistance in Streptococcus pyogenes. Antimicrob. Agents Chemother. 46: 1571-1573 [Abstract] [Full Text]  
  • Saleh-Mghir, A., Ameur, N., Muller-Serieys, C., Ismael, F., Lemaitre, F., Massias, L., Feger, C., Bleton, R., Cremieux, A.-C. (2002). Combination of Quinupristin-Dalfopristin (Synercid) and Rifampin Is Highly Synergistic in Experimental Staphylococcus aureus Joint Prosthesis Infection. Antimicrob. Agents Chemother. 46: 1122-1124 [Abstract] [Full Text]  
  • Vogler, A. J., Busch, J. D., Percy-Fine, S., Tipton-Hunton, C., Smith, K. L., Keim, P. (2002). Molecular Analysis of Rifampin Resistance in Bacillus anthracis and Bacillus cereus. Antimicrob. Agents Chemother. 46: 511-513 [Abstract] [Full Text]  
  • Finan, J. E., Rosato, A. E., Dickinson, T. M., Ko, D., Archer, G. L. (2002). Conversion of Oxacillin-Resistant Staphylococci from Heterotypic to Homotypic Resistance Expression. Antimicrob. Agents Chemother. 46: 24-30 [Abstract] [Full Text]  
  • Fines, M., Pronost, S., Maillard, K., Taouji, S., Leclercq, R. (2001). Characterization of Mutations in the rpoB Gene Associated with Rifampin Resistance in Rhodococcus equi Isolated from Foals. J. Clin. Microbiol. 39: 2784-2787 [Abstract] [Full Text]  
  • Drancourt, M., Carlioz, A., Raoult, D. (2001). rpoB Sequence Analysis of Cultured Tropheryma whippelii. J. Clin. Microbiol. 39: 2425-2430 [Abstract] [Full Text]  
  • Wichelhaus, T. A., Schafer, V., Brade, V., Boddinghaus, B. (2001). Differential effect of rpoB mutations on antibacterial activities of rifampicin and KRM-1648 against Staphylococcus aureus. J Antimicrob Chemother 47: 153-156 [Abstract] [Full Text]  
  • Schmitz, F.-J., Fluit, A. C., Beeck, A., Perdikouli, M., von Eiff, C. (2001). Development of chromosomally encoded resistance mutations in small-colony variants of Staphylococcus aureus. J Antimicrob Chemother 47: 113-115 [Full Text]  
  • Maurin, M., Mersali, N. F., Raoult, D. (2000). Bactericidal Activities of Antibiotics against Intracellular Francisella tularensis. Antimicrob. Agents Chemother. 44: 3428-3431 [Abstract] [Full Text]  
  • Reynolds, M. G. (2000). Compensatory Evolution in Rifampin-Resistant Escherichia coli. Genetics 156: 1471-1481 [Abstract] [Full Text]  
  • O'Neill, A., Oliva, B., Storey, C., Hoyle, A., Fishwick, C., Chopra, I. (2000). RNA Polymerase Inhibitors with Activity against Rifampin-Resistant Mutants of Staphylococcus aureus. Antimicrob. Agents Chemother. 44: 3163-3166 [Abstract] [Full Text]  
  • Schmitz, F.-J., Fluit, A. C., Hafner, D., Beeck, A., Perdikouli, M., Boos, M., Scheuring, S., Verhoef, J., Köhrer, K., Von Eiff, C. (2000). Development of Resistance to Ciprofloxacin, Rifampin, and Mupirocin in Methicillin-Susceptible and -Resistant Staphylococcus aureus Isolates. Antimicrob. Agents Chemother. 44: 3229-3231 [Abstract] [Full Text]  
  • Wichelhaus, T. A., Schäfer, V., Brade, V., Böddinghaus, B. (1999). Molecular Characterization of rpoB Mutations Conferring Cross-Resistance to Rifamycins on Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 43: 2813-2816 [Abstract] [Full Text]  
  • Drancourt, M., Raoult, D. (1999). Characterization of Mutations in the rpoB Gene in Naturally Rifampin-Resistant Rickettsia Species. Antimicrob. Agents Chemother. 43: 2400-2403 [Abstract] [Full Text]  
  • Morse, R., O'Hanlon, K., Virji, M., Collins, M. D. (1999). Isolation of Rifampin-Resistant Mutants of Listeria monocytogenes and Their Characterization by rpoB Gene Sequencing, Temperature Sensitivity for Growth, and Interaction with an Epithelial Cell Line. J. Clin. Microbiol. 37: 2913-2919 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»