Figure 2.

General mechanisms of resistance to polymyxin by lipopolysaccharide (LPS) modifications in Salmonella (mechanisms differ in Pseudomonas). The two-component system PhoQP, activates expression of pmrD. PmrD activates PmrA, which activates cptA and the pmr and arn operons. Along with EptB, CptA modifies the LPS core. The products pmr and arn substitute the phosphates the lipid A portion of the LPS for PEtn and l-Ara4N, respectively. Collectively, the net charge of the outer membrane changes, resulting in repulsion of polymyxin.