GK-11: a Novel Cationic Peptide with Antibiofilm Activity against Staphylococcus aureus and Pseudomonas aeruginosa

Biofilms are implicated in most chronic infections and exhibit up to 1000-fold higher antibiotic resistance than planktonic cells, creating an urgent need for new antibiofilm agents. Here, we characterized GK-11, an 11-amino acid derivative of pleurocidin. Although GK-11 showed limited antimicrobial activity (MIC: 64 µg/mL for Staphylococcus aureus and 256 µg/mL for Pseudomonas aeruginosa), it demonstrated potent antibiofilm effects at sub-MIC levels (MBIC: 32 µg/mL and 16 µg/mL, respectively). Microscopy and SEM confirmed disruption of biofilm structure, while qRT-PCR revealed downregulation of key virulence genes. GK-11 was non-toxic to Caenorhabditis elegans and maintained > 80% viability in human fibroblasts. In vivo, GK-11 improved worm survival against MRSA and PAO1 infection. These results identify GK-11 as a promising, low-toxicity peptide with selective antibiofilm activity for potential therapeutic development.