FIGURE 4.

Mechanisms of Polymyxins-Induced Bacterial Inhibition and Death. (A) The Dab residue of colistin interacts electrostatically with the anionic phosphate group in the outer membrane of bacteria, resulting in structural disruption of the bacterial membrane. (B) Colistin neutralizes the activity of LPS molecules, inhibiting the induction of shock and consequent release of cytokines by immune cells, such as tumor necrosis factor-α and interleukin 8. (C) Colistin binds to phospholipids on the outer membrane of bacteria, causing depletion of phospholipids and leading to bacterial death. (D) Colistin triggers the production of reactive oxygen species (ROS) that damage DNA, lipids, and proteins, ultimately resulting in bacterial death. (E) Colistin inhibits the activity of respiratory enzymes. Permission to reproduce adapted from reference (El-Sayed Ahmed et al., 2020) has been obtained.