Using a diagram of a Gram-negative envelope (outer membrane, periplasmic space with peptidoglycan, inner membrane), indicate the sequence of events after a polymyxin molecule binds the bacterial surface. Which sequence is correct?

Electrostatic binding to LPS → insertion of hydrophobic tail into outer membrane → disruption/permeabilization of outer membrane → penetration to inner membrane and permeabilization → ion leakage and cell death.

Passive diffusion through porins into cytoplasm → inhibition of DNA replication enzymes → accumulation of unrepaired DNA breaks → secondary outer membrane disruption.

Binding to peptidoglycan crosslinks → prevention of cell wall synthesis → immediate outer membrane collapse due to loss of structural crosslinks between membranes and wall.

Enzymatic cleavage of lipids in the periplasm → generation of toxic intermediates that diffuse outward and selectively degrade the outer membrane without affecting the inner membrane.