Assembly of cationic and amphiphilic β-sheet FKF tripeptide confers antibacterial activity.

Abstract The race drawn against bacteria facing the evolution of antimicrobial resistance fuels research for new drugs and therapeutic strategies. FKF, a tripeptide that is cationic and amphiphilic was examined in light of its potential antimicrobial activity. Acid titration of purified peptide solution, 6% w/v (136 mM), yielded a hydrogel at pH∼ 4. Cryo-TEM images of FKF revealed distinct phases formed upon increase in pH, ranging from elongated needles, uniform width fibers, sheets and tubular structures. 1H-NMR attested FKF charged states as function of pH, and CD and FTIR measurements indicated that FKF β-sheet assemblies are held by both π-π stacking and H-bonds. FKF hydrogel displayed bactericidal activity against E. coli and P. aeruginosa with a 3-log reduction in bacterial counts. The hydrogel was also found effective in reducing P. aeruginosa contamination in a skin lesion model in rats. FKF forms a unique antimicrobial peptide-hydrogel, showing neglectable effect in dissolved state, yet only when fibrillary assembled it gains functionality.