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 Sakoulas, G.
Right arrow Articles by Gold, H. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sakoulas, G.
Right arrow Articles by Gold, H. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2002, p. 1492-1502, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1492-1502.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Accessory Gene Regulator (agr) Locus in Geographically Diverse Staphylococcus aureus Isolates with Reduced Susceptibility to Vancomycin

George Sakoulas,1,2* George M. Eliopoulos,1,2 Robert C. Moellering, Jr.,1,2 Christine Wennersten,1 Lata Venkataraman,3 Richard P. Novick,4 and Howard S. Gold1,2

Department of Medicine,1 Division of Laboratory and Transfusion Medicine, Department of Pathology, Beth Israel Deaconess Medical Center,3 Harvard Medical School, Boston, Massachusetts 02115,2 Skirball Institute of Biomolecular Medicine and New York University School of Medicine, New York, New York 100164

Received 10 July 2001/ Returned for modification 12 November 2001/ Accepted 20 January 2002

The majority of infections with glycopeptide intermediate-level resistant Staphylococcus aureus (GISA) originate in biomedical devices, suggesting a possible increased ability of these strains to produce biofilm. Loss of function of the accessory gene regulator (agr) of S. aureus has been suggested to confer an enhanced ability to bind to polystyrene. We studied agr in GISA, hetero-GISA, and related glycopeptide-susceptible S. aureus isolates. All GISA strains from diverse geographic origins belong to agr group II. All GISA strains were defective in agr function, as demonstrated by their inability to produce delta-hemolysin. Hetero-GISA isolate A5940 demonstrated a nonsense mutation in agrA that was not present in a pulsed-field gel electrophoresis-indistinguishable vancomycin-susceptible isolate from the same patient. Various other agr point mutations were noted in several clinical GISA and hetero-GISA isolates. A laboratory-generated agr-null strain demonstrated a small but reproducible increase in vancomycin heteroresistance after growth in vitro in subinhibitory concentrations of vancomycin. This was not seen in the isogenic agr group II parent strain in which agr was intact. The in vitro bactericidal activity of vancomycin was attenuated in the agr-null strain compared to the parent strain. These findings imply that compromised agr function is advantageous to clinical isolates of S. aureus toward the development of vancomycin heteroresistance, perhaps through the development of vancomycin tolerance.

* Corresponding author. Mailing address: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Kennedy Bldg., 6th Floor, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 632-0760. Fax: (617) 632-0766. E-mail: gsakoula{at}caregroup.harvard.edu.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1492-1502, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1492-1502.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kato, Y., Suzuki, T., Ida, T., Maebashi, K. (2009). Genetic changes associated with glycopeptide resistance in Staphylococcus aureus: predominance of amino acid substitutions in YvqF/VraSR. J Antimicrob Chemother 0: dkp394v1-dkp394 [Abstract] [Full Text]  
  • Nguyen, H. M., Graber, C. J. (2009). Limitations of antibiotic options for invasive infections caused by methicillin-resistant Staphylococcus aureus: is combination therapy the answer?. J Antimicrob Chemother 0: dkp377v1-dkp377 [Abstract] [Full Text]  
  • Harigaya, Y., Bulitta, J. B., Forrest, A., Sakoulas, G., Lesse, A. J., Mylotte, J. M., Tsuji, B. T. (2009). Pharmacodynamics of Vancomycin at Simulated Epithelial Lining Fluid Concentrations against Methicillin-Resistant Staphylococcus aureus (MRSA): Implications for Dosing in MRSA Pneumonia. Antimicrob. Agents Chemother. 53: 3894-3901 [Abstract] [Full Text]  
  • Moise, P. A., Smyth, D. S., Robinson, D. A., El-Fawal, N., McCalla, C., Sakoulas, G. (2009). Genotypic and phenotypic relationships among methicillin-resistant Staphylococcus aureus from three multicentre bacteraemia studies. J Antimicrob Chemother 63: 873-876 [Abstract] [Full Text]  
  • Rose, W. E., Poppens, P. T. (2009). Impact of biofilm on the in vitro activity of vancomycin alone and in combination with tigecycline and rifampicin against Staphylococcus aureus. J Antimicrob Chemother 63: 485-488 [Abstract] [Full Text]  
  • Merino, N., Toledo-Arana, A., Vergara-Irigaray, M., Valle, J., Solano, C., Calvo, E., Lopez, J. A., Foster, T. J., Penades, J. R., Lasa, I. (2009). Protein A-Mediated Multicellular Behavior in Staphylococcus aureus. J. Bacteriol. 191: 832-843 [Abstract] [Full Text]  
  • Peerayeh, S. N., Azimian, A., Nejad, Q. B., Kashi, M. (2009). Prevalence of agr Specificity Groups Among Staphylococcus aureus Isolates From University Hospitals in Tehran. Lab Med 40: 27-29 [Abstract] [Full Text]  
  • Delgado, A., Zaman, S., Muthaiyan, A., Nagarajan, V., Elasri, M. O., Wilkinson, B. J., Gustafson, J. E. (2008). The fusidic acid stimulon of Staphylococcus aureus. J Antimicrob Chemother 62: 1207-1214 [Abstract] [Full Text]  
  • Karauzum, H., Ferry, T., de Bentzmann, S., Lina, G., Bes, M., Vandenesch, F., Schmaler, M., Berger-Bachi, B., Etienne, J., Landmann, R. (2008). Comparison of Adhesion and Virulence of Two Predominant Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Clones and Clonal Methicillin-Susceptible S. aureus Isolates. Infect. Immun. 76: 5133-5138 [Abstract] [Full Text]  
  • McCalla, C., Smyth, D. S., Robinson, D. A., Steenbergen, J., Luperchio, S. A., Moise, P. A., Fowler, V. G. Jr., Sakoulas, G. (2008). Microbiological and Genotypic Analysis of Methicillin-Resistant Staphylococcus aureus Bacteremia. Antimicrob. Agents Chemother. 52: 3441-3443 [Abstract] [Full Text]  
  • Rybak, M. J., Leonard, S. N., Rossi, K. L., Cheung, C. M., Sadar, H. S., Jones, R. N. (2008). Characterization of Vancomycin-Heteroresistant Staphylococcus aureus from the Metropolitan Area of Detroit, Michigan, over a 22-Year Period (1986 to 2007). J. Clin. Microbiol. 46: 2950-2954 [Abstract] [Full Text]  
  • Traber, K. E., Lee, E., Benson, S., Corrigan, R., Cantera, M., Shopsin, B., Novick, R. P. (2008). agr function in clinical Staphylococcus aureus isolates. Microbiology 154: 2265-2274 [Abstract] [Full Text]  
  • Leonard, S. N., Cheung, C. M., Rybak, M. J. (2008). Activities of Ceftobiprole, Linezolid, Vancomycin, and Daptomycin against Community-Associated and Hospital-Associated Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 52: 2974-2976 [Abstract] [Full Text]  
  • Chua, T., Moore, C. L., Perri, M. B., Donabedian, S. M., Masch, W., Vager, D., Davis, S. L., Lulek, K., Zimnicki, B., Zervos, M. J. (2008). Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates in Urban Detroit. J. Clin. Microbiol. 46: 2345-2352 [Abstract] [Full Text]  
  • Collins, J., Buckling, A., Massey, R. C. (2008). Identification of Factors Contributing to T-Cell Toxicity of Staphylococcus aureus Clinical Isolates. J. Clin. Microbiol. 46: 2112-2114 [Abstract] [Full Text]  
  • Rose, W. E., Kaatz, G. W., Sakoulas, G., Rybak, M. J. (2008). Teicoplanin pharmacodynamics in reference to the accessory gene regulator (agr) in Staphylococcus aureus using an in vitro pharmacodynamic model. J Antimicrob Chemother 61: 1099-1102 [Abstract] [Full Text]  
  • Chi, C.-Y., Lauderdale, T.-L., Wang, S.-M., Wu, J.-M., Yang, Y.-J., Liu, C.-C. (2008). Health Care-Associated Endocarditis Caused by Staphylococcus aureus with Reduced Susceptibility to Vancomycin. J. Clin. Microbiol. 46: 810-813 [Abstract] [Full Text]  
  • Moise, P. A., Smyth, D. S., El-Fawal, N., Robinson, D. A., Holden, P. N., Forrest, A., Sakoulas, G. (2008). Microbiological effects of prior vancomycin use in patients with methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother 61: 85-90 [Abstract] [Full Text]  
  • Sakoulas, G., Rose, W., Rybak, M. J., Pillai, S., Alder, J., Moellering, R. C. Jr., Eliopoulos, G. M. (2008). Evaluation of Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus Developing Nonsusceptibility to Daptomycin. J. Clin. Microbiol. 46: 220-224 [Abstract] [Full Text]  
  • Yarwood, J. M., Paquette, K. M., Tikh, I. B., Volper, E. M., Greenberg, E. P. (2007). Generation of Virulence Factor Variants in Staphylococcus aureus Biofilms. J. Bacteriol. 189: 7961-7967 [Abstract] [Full Text]  
  • Rossney, A. S., Shore, A. C., Morgan, P. M., Fitzgibbon, M. M., O'Connell, B., Coleman, D. C. (2007). The Emergence and Importation of Diverse Genotypes of Methicillin-Resistant Staphylococcus aureus (MRSA) Harboring the Panton-Valentine Leukocidin Gene (pvl) Reveal that pvl Is a Poor Marker for Community-Acquired MRSA Strains in Ireland. J. Clin. Microbiol. 45: 2554-2563 [Abstract] [Full Text]  
  • Moise, P. A., Sakoulas, G., Forrest, A., Schentag, J. J. (2007). Vancomycin In Vitro Bactericidal Activity and Its Relationship to Efficacy in Clearance of Methicillin-Resistant Staphylococcus aureus Bacteremia. Antimicrob. Agents Chemother. 51: 2582-2586 [Abstract] [Full Text]  
  • Pillai, S. K., Gold, H. S., Sakoulas, G., Wennersten, C., Moellering, R. C. Jr., Eliopoulos, G. M. (2007). Daptomycin Nonsusceptibility in Staphylococcus aureus with Reduced Vancomycin Susceptibility Is Independent of Alterations in MprF. Antimicrob. Agents Chemother. 51: 2223-2225 [Abstract] [Full Text]  
  • Rose, W. E., Rybak, M. J., Tsuji, B. T., Kaatz, G. W., Sakoulas, G. (2007). Correlation of vancomycin and daptomycin susceptibility in Staphylococcus aureus in reference to accessory gene regulator (agr) polymorphism and function. J Antimicrob Chemother 59: 1190-1193 [Abstract] [Full Text]  
  • Mwangi, M. M., Wu, S. W., Zhou, Y., Sieradzki, K., de Lencastre, H., Richardson, P., Bruce, D., Rubin, E., Myers, E., Siggia, E. D., Tomasz, A. (2007). Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing. Proc. Natl. Acad. Sci. USA 104: 9451-9456 [Abstract] [Full Text]  
  • Tsuji, B. T., Rybak, M. J., Lau, K. L., Sakoulas, G. (2007). Evaluation of Accessory Gene Regulator (agr) Group and Function in the Proclivity towards Vancomycin Intermediate Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 51: 1089-1091 [Abstract] [Full Text]  
  • Luczak-Kadlubowska, A., Krzyszton-Russjan, J., Hryniewicz, W. (2006). Characteristics of Staphylococcus aureus Strains Isolated in Poland in 1996 to 2004 That Were Deficient in Species-Specific Proteins. J. Clin. Microbiol. 44: 4018-4024 [Abstract] [Full Text]  
  • Howden, B. P., Johnson, P. D. R., Ward, P. B., Stinear, T. P., Davies, J. K. (2006). Isolates with Low-Level Vancomycin Resistance Associated with Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia.. Antimicrob. Agents Chemother. 50: 3039-3047 [Abstract] [Full Text]  
  • de Araujo, G. L., Coelho, L. R., de Carvalho, C. B., Maciel, R. M., Coronado, A. Z., Rozenbaum, R., Ferreira-Carvalho, B. T., Sa Figueiredo, A. M., Teixeira, L. A. (2006). Commensal isolates of methicillin-resistant Staphylococcus epidermidis are also well equipped to produce biofilm on polystyrene surfaces. J Antimicrob Chemother 57: 855-864 [Abstract] [Full Text]  
  • Sakoulas, G., Alder, J., Thauvin-Eliopoulos, C., Moellering, R. C. Jr., Eliopoulos, G. M. (2006). Induction of Daptomycin Heterogeneous Susceptibility in Staphylococcus aureus by Exposure to Vancomycin.. Antimicrob. Agents Chemother. 50: 1581-1585 [Abstract] [Full Text]  
  • Sakoulas, G., Gold, H. S., Cohen, R. A., Venkataraman, L., Moellering, R. C., Eliopoulos, G. M. (2006). Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia. J Antimicrob Chemother 57: 699-704 [Abstract] [Full Text]  
  • McAleese, F., Wu, S. W., Sieradzki, K., Dunman, P., Murphy, E., Projan, S., Tomasz, A. (2006). Overexpression of Genes of the Cell Wall Stimulon in Clinical Isolates of Staphylococcus aureus Exhibiting Vancomycin-Intermediate- S. aureus-Type Resistance to Vancomycin. J. Bacteriol. 188: 1120-1133 [Abstract] [Full Text]  
  • Robinson, D. A., Monk, A. B., Cooper, J. E., Feil, E. J., Enright, M. C. (2005). Evolutionary Genetics of the Accessory Gene Regulator (agr) Locus in Staphylococcus aureus. J. Bacteriol. 187: 8312-8321 [Abstract] [Full Text]  
  • Wright, J. S. III, Traber, K. E., Corrigan, R., Benson, S. A., Musser, J. M., Novick, R. P. (2005). The agr Radiation: an Early Event in the Evolution of Staphylococci. J. Bacteriol. 187: 5585-5594 [Abstract] [Full Text]  
  • Cui, L., Lian, J.-Q., Neoh, H.-m., Reyes, E., Hiramatsu, K. (2005). DNA Microarray-Based Identification of Genes Associated with Glycopeptide Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 49: 3404-3413 [Abstract] [Full Text]  
  • Sakoulas, G., Eliopoulos, G. M., Fowler, V. G. Jr., Moellering, R. C. Jr., Novick, R. P., Lucindo, N., Yeaman, M. R., Bayer, A. S. (2005). Reduced Susceptibility of Staphylococcus aureus to Vancomycin and Platelet Microbicidal Protein Correlates with Defective Autolysis and Loss of Accessory Gene Regulator (agr) Function. Antimicrob. Agents Chemother. 49: 2687-2692 [Abstract] [Full Text]  
  • Li, D., Renzoni, A., Estoppey, T., Bisognano, C., Francois, P., Kelley, W. L., Lew, D. P., Schrenzel, J., Vaudaux, P. (2005). Induction of Fibronectin Adhesins in Quinolone-Resistant Staphylococcus aureus by Subinhibitory Levels of Ciprofloxacin or by Sigma B Transcription Factor Activity Is Mediated by Two Separate Pathways. Antimicrob. Agents Chemother. 49: 916-924 [Abstract] [Full Text]  
  • Dunman, P. M., Mounts, W., McAleese, F., Immermann, F., Macapagal, D., Marsilio, E., McDougal, L., Tenover, F. C., Bradford, P. A., Petersen, P. J., Projan, S. J., Murphy, E. (2004). Uses of Staphylococcus aureus GeneChips in Genotyping and Genetic Composition Analysis. J. Clin. Microbiol. 42: 4275-4283 [Abstract] [Full Text]  
  • Renzoni, A., Francois, P., Li, D., Kelley, W. L., Lew, D. P., Vaudaux, P., Schrenzel, J. (2004). Modulation of Fibronectin Adhesins and Other Virulence Factors in a Teicoplanin-Resistant Derivative of Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 48: 2958-2965 [Abstract] [Full Text]  
  • Adhikari, R. P., Scales, G. C., Kobayashi, K., Smith, J. M. B., Berger-Bachi, B., Cook, G. M. (2004). Vancomycin-induced deletion of the methicillin resistance gene mecA in Staphylococcus aureus. J Antimicrob Chemother 54: 360-363 [Abstract] [Full Text]  
  • Maki, H., McCallum, N., Bischoff, M., Wada, A., Berger-Bachi, B. (2004). tcaA Inactivation Increases Glycopeptide Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 48: 1953-1959 [Abstract] [Full Text]  
  • Verdier, I., Reverdy, M.-E., Etienne, J., Lina, G., Bes, M., Vandenesch, F. (2004). Staphylococcus aureus Isolates with Reduced Susceptibility to Glycopeptides Belong to Accessory Gene Regulator Group I or II. Antimicrob. Agents Chemother. 48: 1024-1027 [Abstract] [Full Text]  
  • Lim, Y., Jana, M., Luong, T. T., Lee, C. Y. (2004). Control of Glucose- and NaCl-Induced Biofilm Formation by rbf in Staphylococcus aureus. J. Bacteriol. 186: 722-729 [Abstract] [Full Text]  
  • Rossi, J., Bischoff, M., Wada, A., Berger-Bachi, B. (2003). MsrR, a Putative Cell Envelope-Associated Element Involved in Staphylococcus aureus sarA Attenuation. Antimicrob. Agents Chemother. 47: 2558-2564 [Abstract] [Full Text]  
  • Mongodin, E., Finan, J., Climo, M. W., Rosato, A., Gill, S., Archer, G. L. (2003). Microarray Transcription Analysis of Clinical Staphylococcus aureus Isolates Resistant to Vancomycin. J. Bacteriol. 185: 4638-4643 [Abstract] [Full Text]  
  • Gustafson, J. E., O'Brien, F. G., Coombs, G. W., Malkowski, M. J., Grubb, W. B., Pfeltz, R. F., Wilkinson, B. J. (2003). Alterations in phage-typing patterns in vancomycin-intermediate Staphylococcus aureus. J Med Microbiol 52: 711-714 [Abstract] [Full Text]  
  • Reipert, A., Ehlert, K., Kast, T., Bierbaum, G. (2003). Morphological and Genetic Differences in Two Isogenic Staphylococcus aureus Strains with Decreased Susceptibilities to Vancomycin. Antimicrob. Agents Chemother. 47: 568-576 [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]  
  • Price, C. T. D., Singh, V. K., Jayaswal, R. K., Wilkinson, B. J., Gustafson, J. E. (2002). Pine Oil Cleaner-Resistant Staphylococcus aureus: Reduced Susceptibility to Vancomycin and Oxacillin and Involvement of SigB. Appl. Environ. Microbiol. 68: 5417-5421 [Abstract] [Full Text]  
  • Pillai, S. K., Sakoulas, G., Gold, H. S., Wennersten, C., Eliopoulos, G. M., Moellering, R. C. Jr., Inouye, R. T. (2002). Prevalence of the fsr Locus in Enterococcus faecalis Infections. J. Clin. Microbiol. 40: 2651-2652 [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»