Dermcidin-derived peptides inhibit `P. aeruginosa` and `S. aureus` biofilm formation and disrupt mature biofilms

The escalating crisis of antimicrobial resistance (AMR), particularly in opportunistic pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, poses a significant challenge in clinical settings. These bacteria frequently form persistent biofilms on medical devices and host tissues, rendering them highly resistant to conventional antibiotics and host immune responses. Current treatments often fall short against these entrenched infections, necessitating novel therapeutic strategies. Dermcidin, an endogenous human antimicrobial peptide, offers a promising alternative by targeting bacterial virulence and biofilm development, rather than solely relying on bactericidal effects.

Researchers investigated the antimicrobial and anti-biofilm properties of three dermcidin-derived peptides (DCD-1L, SSL-23, and SSL-25) against clinical isolates. The study included methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA), alongside carbapenem-susceptible and carbapenem-resistant P. aeruginosa (CSPA and CRPA). The peptides' inhibitory activity on bacterial adhesion and biofilm formation was assessed at sub-MIC levels (1/2, 1/4, and 1/8 MIC). Their ability to disrupt mature biofilms was evaluated at higher concentrations (8x-64x MIC). Furthermore, qRT-PCR was used to quantify the expression of key biofilm-associated and quorum-sensing genes following peptide exposure.

Dermcidin-derived peptides demonstrated potent activity against both P. aeruginosa and S. aureus clinical isolates. They markedly inhibited bacterial attachment and biofilm formation at sub-inhibitory concentrations, specifically at 1/2, 1/4, and 1/8 MIC. Beyond prevention, the peptides also exhibited strong biofilm eradication activity, effectively disrupting established mature biofilms when applied at higher concentrations ranging from 8x to 64x MIC. Gene expression analysis provided mechanistic insights, revealing a significant down-regulation of adhesion-related genes and quorum-sensing-related genes in both S. aureus and P. aeruginosa following treatment with the peptides. This suggests a multi-modal action, targeting both initial attachment and the coordinated community behavior essential for biofilm maturation. The findings indicate that these peptides' efficacy is independent of their net charge.

Dermcidin-derived peptides markedly inhibited bacterial attachment and biofilm formation at sub-inhibitory concentrations (1/2, 1/4, and 1/8 MIC), and exhibited strong biofilm eradication activity at higher concentrations (8x-64x MIC).