The addition of 4-amino-4-deoxy-L-arabinose (L-Ara4N) by enzymes such as ColRS or PmrAB (Figure ) is another common modification conferring resistance to polymyxins . This bulky cationic sugar masks Lipid A phosphates (Fig. ), thereby repelling cationic AMPs . Unlike pEtN [112], L-Ara4N lacks Ca 2+ -bridging properties but efficiently repels AMPs through charge shielding . In some cases, L-Ara4N and pEtN coexist in the same LPS molecule, sometimes accompanied by additional palmitate acyl chains, creating LPS structures highly resistant to polymixins via three synergistic mechanisms: enhanced LPS-LPS interactions, charge repulsion, and improved hydrophobic packing . While L-Ara4N is often attached to the Lipid A phosphates, in some species (e.g., Proteus mirabilis) it can also be attached to the Kdo residues of the core sugars . Additionally, hydroxylation of Lipid A acyl chains enables subsequent esterification reactions that incorporate new acyl chains . This modification significantly increases membrane hydrophobicity and packing density, impeding the penetration of cationic AMPs. Notably, these more heavily acylated Lipid A variants are typically more immunogenic , highlighting a trade-off where increased AMP resistance is achieved at the expense of immune evasion.