| Summary: | Colistin is a last-resort antimicrobial agent for treating carbapenem-resistant <i>Acinetobacter baumannii</i> infections. The activation of PmrAB by several environmental signals induces colistin resistance in Gram-negative bacteria. This study investigated the molecular mechanisms of colistin resistance in <i>A. baumannii</i> under acidic conditions using wild-type (WT) <i>A. baumannii</i> 17978, Δ<i>pmrA</i> and Δ<i>pmrB</i> mutants, and <i>pmrA</i>-complemented strains. The <i>pmrA</i> or <i>pmrB</i> deletion did not affect the growth of <i>A. baumannii</i> under acidic or aerobic conditions. <i>A. baumannii</i> under acidic (pH 5.5) and high-iron (1 mM) conditions showed 32- and 8-fold increases in the minimum inhibitory concentrations (MICs) of colistin, respectively. The Δ<i>pmrA</i> and Δ<i>pmrB</i> mutants at pH 5.5 showed a significant decrease in colistin MICs compared to the WT strain at pH 5.5. No difference in colistin MICs was observed between WT and mutant strains under high-iron conditions. The <i>pmrCAB</i> expression significantly increased in the WT strain at pH 5.5 compared to the WT strain at pH 7.0. The <i>pmrC</i> expression significantly decreased in two mutant strains at pH 5.5 compared to the WT strain at pH 5.5. The PmrA protein was expressed in the Δ<i>pmrA</i> strain carrying ppmrA_FLAG plasmids at pH 5.5 but not at pH 7.0. Lipid A modification by the addition of phosphoethanolamine was observed in the WT strain at pH 5.5. In conclusion, this study demonstrated that <i>A. baumannii</i> under acidic conditions induces colistin resistance via the activation of <i>pmrCAB</i> operon and subsequent lipid A modification.
|
|---|