Shigella flexneri also demonstrates a notable mechanism of resistance to cationic AMPs at the O-antigen level. Typically, the O-antigen of S. flexneri consists of 4-5 sugar residues, three of which are L-rhamnose. The serotypes Xv and Yv incorporate 1 and 2 pEtN substitutions, respectively, into the rhamnose residues of each O-antigen repeat . These pEtN moieties strengthen bridging between O-antigen repeat units, facilitated by divalent cations, forming an extensive interaction network that extends across . This dense barrier significantly impedes AMP penetration. Furthermore, these new S. flexneri serotypes evade immune recognition, presenting challenges for both antibiotic and vaccine development .