Evolutionary mapping of the SHV β-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 bla(SHV). Materials and methods: Evolutionary mapping used a shortest-path analysis of aligned bla(SHV) variants, and other basic bioinformatic approaches, such as CLUSTAL W and Blast were employed. Results: Two main branches of the bla(SHV) evolutionary tree were located; both are derived from variant bla(SHV)-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 bla(SHV) framework sequences. Analysis of the genome sequence of Klebsiella pneumoniae confirms the chromosomal origin of bla(SHV), 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 bla(SHV) 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 bla(SHV), and these observations may be useful in predicting what might happen in future, both for bla(SHV), and for other beta-lactamase genes.