Evolutionary mapping of the SHV beta-lactamase and evidence for two separate IS26-dependent blaSHV mobilization events from the Klebsiella pneumoniae chromosome.

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 beta-lactamase genes.