Correlation between overexpression and amino acid substitution of the PmrAB locus and colistin resistance in Acinetobacter baumannii

Relationships between the PmrAB two-component system and colistin resistance were investigated in Acinetobacter baumannii. The sequences of pmrA, pmrB and pmrC in 26 colistin-susceptible (ColS) and 7 colistin-resistant (ColR) A. baumannii isolates were determined. In addition, 30 ColR mutants (colistin minimum inhibitory concentration >64 mg/L) were selected in vitro from 10 ColS strains and the pmrA, pmrB and pmrC sequences of the in-vitro-selected ColR mutants were also determined. Expression of pmrA and pmrB was compared between the ColR mutants and their parent ColS strains using a quantitative real-time polymerase chain reaction method. Elevated expression of pmrA and pmrB genes was evident both in wild-type and in in-vitro-selected ColR strains. However, no amino acid differences in the pmrA, pmrB and pmrC genes were found between wild-type ColR and ColS isolates. Although six kinds of amino acid alterations in pmrB were identified in in-vitro-selected ColR mutants, no changes were found in some of the mutants. These findings indicate that increased expression of the PmrAB system is essential for colistin resistance in A. baumannii but that amino acid alterations might be only partially responsible for resistance.