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*Staphylococcal Infections

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Journal of Bacteriology, June 2003, p. 3307-3316, Vol. 185, No. 11
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.11.3307-3316.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

How Clonal Is Staphylococcus aureus?

Edward J. Feil,1* Jessica E. Cooper,1 Hajo Grundmann,2 D. Ashley Robinson,1 Mark C. Enright,1 Tony Berendt,3 Sharon J. Peacock,4 John Maynard Smith,5 Michael Murphy,6 Brian G. Spratt,7 Catrin E. Moore,3 and Nicholas P. J. Day3

Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY,1 Microbiology and Infectious Diseases, Queen's Medical Centre, University Hospital Nottingham, Nottingham NG7 2UH,2 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine,3 Nuffield Department of Clinical Laboratory Sciences, University of Oxford,4 National Blood Service, John Radcliffe Hospital, Oxford OX3 9DU,6 School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG,5 Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, St. Mary's Hospital, London W2 1PG, United Kingdom7

Received 6 January 2003/ Accepted 17 March 2003

Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable "core" genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.

* Corresponding author. Mailing address: Department of Biology and Biochemistry, University of Bath, 4 South, Claverton Down, Bath BA2 7AY, United Kingdom. Phone: 44 (0) 1225 383021. Fax: 44 (0) 1225 386779. E-mail: e.feil{at}bath.ac.uk.

Journal of Bacteriology, June 2003, p. 3307-3316, Vol. 185, No. 11
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.11.3307-3316.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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