Journal of Antimicrobial Chemotherapy (2002) 49, 255-260
© 2002 The British Society for Antimicrobial Chemotherapy
Preliminary analysis of the genetic basis for vancomycin resistance in Staphylococcus aureus strain Mu50
a Bristol Centre for Antimicrobial Research and Evaluation, Departments of Biochemistry and b Pathology & Microbiology, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD; c Department of Medical Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK
Glycopeptides, such as vancomycin, are frequently the antibiotics of choice for treatment of infections caused by the now common methicillin-resistant Staphylococcus aureus (MRSA). Incidences of vancomycin resistance in S. aureus (VRSA) have been increasing worldwide for the last 5 years. Complex mechanisms producing changes in cell wall content and composition generate the VRSA phenotype, but the genetic basis of these changes has not yet been determined. To facilitate the genetic investigation, entire genome sequences of the archetypal VRSA (Mu50), and vancomycin-susceptible MRSA strains N315, EMRSA 16 and COL were compared. The in silico analysis revealed several loss-of-function mutations in Mu50, affecting important cell wall biosynthesis and intermediary metabolism genes, not previously reported. The new findings provide further evidence for the hypothesis that vancomycin resistance in Mu50 is due to fundamental changes, important to metabolic pathways that impinge on peptidoglycan biosynthesis. These observations will inform targeted experiments aimed at a complete understanding of the mechanism(s) of vancomycin resistance in S. aureus Mu50 and other VRSA strains.
* Corresponding author. Tel: +44-117-928-7439; Fax: +44-117-928-8274; E-mail: Matthewb.Avison{at}bris.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. M. Mwangi, S. W. Wu, Y. Zhou, K. Sieradzki, H. de Lencastre, P. Richardson, D. Bruce, E. Rubin, E. Myers, E. D. Siggia, et al. Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing PNAS, May 29, 2007; 104(22): 9451 - 9456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. J. B. Sibbald, A. K. Ziebandt, S. Engelmann, M. Hecker, A. de Jong, H. J. M. Harmsen, G. C. Raangs, I. Stokroos, J. P. Arends, J. Y. F. Dubois, et al. Mapping the Pathways to Staphylococcal Pathogenesis by Comparative Secretomics Microbiol. Mol. Biol. Rev., September 1, 2006; 70(3): 755 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. J. Brown, D. I. Edwards, P. M. Hawkey, D. Morrison, G. L. Ridgway, K. J. Towner, M. W. D. Wren, and on behalf of the Joint Working Party of the Britis Guidelines for the laboratory diagnosis and susceptibility testing of methicillin-resistant Staphylococcus aureus (MRSA) J. Antimicrob. Chemother., December 1, 2005; 56(6): 1000 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Kusuma and J. F. Kokai-Kun Comparison of Four Methods for Determining Lysostaphin Susceptibility of Various Strains of Staphylococcus aureus Antimicrob. Agents Chemother., August 1, 2005; 49(8): 3256 - 3263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Koehl, A. Muthaiyan, R. K. Jayaswal, K. Ehlert, H. Labischinski, and B. J. Wilkinson Cell Wall Composition and Decreased Autolytic Activity and Lysostaphin Susceptibility of Glycopeptide-Intermediate Staphylococcus aureus Antimicrob. Agents Chemother., October 1, 2004; 48(10): 3749 - 3757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Muthaiyan, R. K. Jayaswal, and B. J. Wilkinson Intact mutS in Laboratory-Derived and Clinical Glycopeptide-Intermediate Staphylococcus aureus Strains Antimicrob. Agents Chemother., February 1, 2004; 48(2): 623 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wootton, M. B. Avison, P. M. Bennett, R. A. Howe, A. P. MacGowan, and T. R. Walsh Genetic analysis of 17 genes in Staphylococcus aureus with reduced susceptibility to vancomycin (VISA) and heteroVISA J. Antimicrob. Chemother., February 1, 2004; 53(2): 406 - 407. [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Gustafson, F. G. O'Brien, G. W. Coombs, M. J. Malkowski, W. B. Grubb, R. F. Pfeltz, and B. J. Wilkinson Alterations in phage-typing patterns in vancomycin-intermediate Staphylococcus aureus J. Med. Microbiol., August 1, 2003; 52(8): 711 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. O'Neill, I. Chopra, G. Bierbaum, A. Reipert, and F. Schaaff Lack of Evidence for Involvement of Hypermutability in Emergence of Vancomycin-Intermediate Staphylococcus aureus Antimicrob. Agents Chemother., April 1, 2003; 47(4): 1484 - 1485. [Full Text] [PDF]
|
|
|
|
|
|
R. W. Ellis Mu50 glycopeptide-resistant Staphylococcus aureus: the case of the missing penicillinase J. Antimicrob. Chemother., March 1, 2003; 51(3): 739 - 740. [Full Text] [PDF]
|
|
|
|
|
|
A. Reipert, K. Ehlert, T. Kast, and G. Bierbaum Morphological and Genetic Differences in Two Isogenic Staphylococcus aureus Strains with Decreased Susceptibilities to Vancomycin Antimicrob. Agents Chemother., February 1, 2003; 47(2): 568 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Schaaff, A. Reipert, and G. Bierbaum An Elevated Mutation Frequency Favors Development of Vancomycin Resistance in Staphylococcus aureus Antimicrob. Agents Chemother., November 1, 2002; 46(11): 3540 - 3548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. O'Neill and I. Chopra 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., August 1, 2002; 50(2): 161 - 169. [Abstract] [Full Text] [PDF]
|
|