Fig. 8: Schematics of the action pathways of Dap on Gram+ membranes.

The timescale is indicated. The insertion of Dap molecules in the membrane rises the pressure. The pressure relief drives Dap actions: Left, When the membrane does not contain CL, the formation of Dap oligomers is followed by the formation of dimples in the membrane, followed by the formation of elongated-humps. The dimples favour the translocation of Dap to the inner membrane leaflet by the flip-flop mechanism. When Dap is present in the inner and outer leaflets toroidal pores form, the membrane is permeated, and the bacteria die. Alternatively, Dap can also induce ejection of material from the membrane by the formation of tubulations; equally destabilising the membrane and killing the bacteria. Right, Concerning the bacteria containing a high content of CL in the membrane (>20% molar), Dap action is drastically modified. In this case, the Dap flip-flop does not take place and the dimples are not formed. Instead, the membrane buckles but it does not break. Hence, despite Dap insertion, the membrane still separates the cytoplasm from the exterior. In the improbable case that some Dap molecules reach the inner leaflet of the membrane, pores form as in the case CL is present. The particularity of the pores formed under high CL content is that they are able of ejecting material out of the membrane. These pores behave ‘like geysers’, and relief the pressure built on the outer leaflet by the insertions of Dap molecules in cycles of activity. Both CL-related processes maintain the membrane integrity and the bacteria alive.