摘要：Ineffectiveness of carbapenems against multidrug resistant pathogens led to the increased use of colistin (polymyxin E) as a last resort antibiotic. A gene belonging to the DedA family encoding conserved membrane proteins was previously identified by screening a transposon library of
K. pneumoniae ST258 for sensitivity to colistin. We have renamed this gene
dkcA (
d
edA of
K
lebsiella required for
colistin resistance). DedA family proteins are likely membrane transporters required for viability of
Escherichia coli and
Burkholderia spp. at alkaline pH and for resistance to colistin in a number of bacterial species. Colistin resistance is often conferred via modification of the lipid A component of bacterial lipopolysaccharide with aminoarabinose (Ara4N) and/or phosphoethanolamine. Mass spectrometry analysis of lipid A of the
∆dkcA mutant shows a near absence of Ara4N in the lipid A, suggesting a requirement for DkcA for lipid A modification with Ara4N. Mutation of
K. pneumoniae dkcA resulted in a reduction of the colistin minimal inhibitory concentration to approximately what is found with a Δ
arnT strain. We also identify a requirement of DkcA for colistin resistance that is independent of lipid A modification, instead requiring maintenance of optimal membrane potential.
K. pneumoniae Δ
dkcA displays reduced virulence in
Galleria mellonella suggesting colistin sensitivity can cause loss of virulence.
