Antibacterial Mechanisms of Polymyxin and Bacterial Resistance

Figure 3

Hydroxyl radical death mechanism in bacteria induced by polymyxin [46]. The polymyxin molecule (magenta) comes across inner membrane (IM) and induces (superoxide) generation. Then, will be converted to H₂O₂ by SOD (superoxide dismutase). Both and H₂O₂ can oxidatively attack Fe-S (iron-sulfur) clusters (iron and sulfur are shown as red and purple points, resp.) and cause inactivation of Fe-S cluster (from light cyan to dark blue) and iron leaching. With the conversion of “free” ferrous iron (Fe²⁺) to ferric iron (Fe³⁺), H₂O₂, via Fenton reaction, will be rapidly converted to ^•OH (hydroxyl radical) which readily damages DNA, lipids, and proteins.