JAC Advance Access published online on May 26, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh251
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 Bristol Centre for Antimicrobial Research and Evaluation, Bacterial Genomics Group, Department of Pathology & Microbiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK
* To whom correspondence should be addressed. E-mail: matthewb.avison{at}bris.ac.uk.
Objectives: To determine the most likely evolutionary pathway that has led to the development of extended-spectrum SHV derivatives, and to the mobilization of blaSHV. Materials and methods: Evolutionary mapping used a shortest-path analysis of aligned blaSHV variants, and other basic bioinformatic approaches, such as CLUSTAL W and Blast were employed. Results: Two main branches of the blaSHV evolutionary tree were located; both are derived from variant blaSHV-1 alleles. Identical mutations, responsible for extended-spectrum SHV substrate profiles, have been selected independently in each branch. There is evidence for a pool of non-mobile blaSHV framework sequences. Analysis of the genome sequence of Klebsiella pneumoniae confirms the chromosomal origin of blaSHV, whose mobilization has occurred at least twice, once for each of the main evolutionary branches. Both these mobilization events have been catalysed by IS26. Evolution of blaSHV to give common extended-spectrum variants is most likely to have occurred following mobilization. Conclusions: These data shed new light on the evolution and mobilization of blaSHV, and these observations may be useful in predicting what might happen in future, both for blaSHV, and for other
Revised March 24, 2004
Accepted March 30, 2004
Original article
Evolutionary mapping of the SHV
-lactamase and evidence for two separate IS26-dependent blaSHV mobilization events from the Klebsiella pneumoniae chromosome
Abstract 
-lactamase genes.
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