Antibacterial Mechanisms of Polymyxin and Bacterial Resistance

Figure 4

PhoP-PhoQ two-component system of bacterial resistance to polymyxin [57]. PhoP is phosphorylated by PhoP-PhoQ system under low Mg²⁺, low pH, and polymyxin, promoting pmrD gene to express PmrD protein. With the help of PmrD and in the presence of Fe³⁺, transcription of PmrA-activated gene is induced by PmrA-PmrB system. After phosphorylation, PmrA-P activates transcription of LPS modification loci (i.e., Wzz, PmrG, CptA, ugd, pbgP, and pmrC). The O-antigen synthesis is controlled by products of wzz gene. The PmrG and CptA proteins are responsible for the phosphorylation modification of heptose (I) and heptose (II) (blue segments), respectively. Lipid A (red part) can be phosphorylated with phosphoethanolamine (pEtN) encoded by PmrC or L-4-aminoarabinose (L-Ara4N) encoded by Ugd and PbgP. P: phosphorylated.