Twenty three K. pneumoniae (blaDHA-1) clinical isolates exhibited a range of susceptibilities to LYS228, with MICs of ≥8 μg/mL for 9 of these. Mutants with decreased susceptibility to LYS228 and upregulated expression of blaDHA-1 were selected from representative isolates. These had mutations in the chromosomal peptidoglycan recycling genes mpl or ampD. Pre-existing mpl mutations were also found in some of the clinical isolates examined and these had strongly upregulated expression of blaDHA-1.
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