Impact of inducible on susceptibility of clinical isolates to LYS228 and identification of chromosomal and mutations mediating upregulation of plasmid borne expression.

Twenty-three Klebsiella pneumoniae (bla(DHA-1)) clinical isolates exhibited a range of susceptibilities to LYS228, with MICs of >= 8 mu g/ml for 9 of these. Mutants with decreased susceptibility to LYS228 and upregulated expression of bla(DHA-1) were selected from representative isolates. These had mutations in the chromosomal peptidoglycan recycling gene mpl or ampD. Preexisting mpl mutations were also found in some of the clinical isolates examined, and these had strongly upregulated expression of bla(DHA-1).