Tryptophan-substituted antimicrobial peptide temporin-1CEb: in vitro and in vivo antibacterial activity against clinically isolated multidrug-resistant Klebsiella pneumoniae

• Trp-substituted temporin-1CEb analogs, particularly I1WL5W, exhibit potent antibacterial activity against multidrug-resistant Klebsiella pneumoniae (MDRKP) with low cytotoxicity. • The antibacterial mechanism involves membrane disruption through surface charge neutralization, membrane insertion, and increased permeability of inner and outer membranes. • Trp-containing peptides inhibit biofilm formation and degrade preformed biofilms by reducing exopolysaccharide production. • In a murine lung infection model, I1WL5W treatment reduces bacterial load and inflammatory cytokines (IL-6, TNF-α), improving lung tissue structure.