Figure 1.

The possible bacteriostatic mechanisms of melatonin in vitro. Melatonin inhibits the growth of bacteria through these avenues: reducing cytoplasmic availability of metal ion (A); interfering cell wall formation, for example, melatonin restricts the absorb of Linoleic acid (LA), which makes up the cell wall, thus limiting cell proliferation (B); melatonin can also regulate the expressions of genes associated with cell division (C) or suppress the content and activity of metabolism-related enzymes (D) to inhibit bacterial growth and proliferation; melatonin resists against Gram-negative bacteria through inhibiting bacterial citrate synthase and reducing the synthesis of citric acid (E), besides, when melatonin is combination with colistin, bacterial outer membrane permeability and oxidative damage are enhanced, and the effect of efflux pumps is inhibited (F), leading to increased bacteria damage. Note: minus in parentheses represents decrease; plus in parentheses represents increase; and the red line represents inhibition; the black arrow indicates activation.