Polymyxins: MD simulations as magnifying lenses over the LPS. Polymyxins are poly-cationic cyclic peptides produced by the soil bacterium Paenibacillus polymyxa [108], and they are known for their potent activity against Gram-negative bacteria, exerting a membrane-mediated mechanism of action . Polymyxins B and E (known as PMB and Colistin, respectively) have been widely for their ability to interact with lipopolysaccharide (LPS) molecules and to penetrate the outer membrane (OM) of Gram-negative bacteria. PMB first binds to the LPS and then forms pores in the outer membrane. The size of the PMB-induced pores depends on the chemical decoration of the LPS, summarized in Figure . In the case of E. Coli or S. Enterica, the pores are large enough to allow self-promoted uptake of PMB . In contrast, inclusion of 4-amino-4-deoxy-L-arabinose at the Kdo of the LPS of P. mirabilis (highlighted in Figure ) leads to a reduction in pore size, with consequent inhibition of the self-uptake mechanism and resulting in strain resistance .