This strategy opens new possibilities for expanding the application of glycopeptides and lantibiotics, both of which typically lack activity against Gram-negative bacteria due to OM impermeability. Glycopeptides and lantibiotics exhibit dual mechanisms of action, combining cell wall synthesis inhibition with membrane-disrupting properties, which not only increases their antibacterial efficacy but also reduces the likelihood of resistance development. When used in combination with OM-permeabilizing agents, these bi-functional antibiotics could potentially overcome barriers to Gram-negative susceptibility.