A strong attractive force between antibiotics and lipopolysaccharide (LPS, a supramolecule also referred to as endotoxin) from bacterial debris was found that can neutralize the intended function of antibiotics and potentially increase the antibacterial dose. The competition between bacteria and LPS was interrupted by the intervention of a supramolecular trap, helping polymyxin family (e.g. colistin), a last-line antibiotic for defense against invasion by gram-negative bacteria (GNB), to escape being hijacked by LPS. The supramolecular trap fabricated from a subnanometer nanosheet can seal off the active site (lipid A) of LPS to directly interrupt the strong attraction, which can minimize endotoxemia and maximize the colistin activity to achieve greater anti-bacterial efficacy. Thus, the potential crisis of colistin abuse and resistance can potentially be avoided.
