Unveiling the Self-assembly and Therapeutic Efficacy of Antimicrobial Peptides SA4 Against Multidrug-Resistant A. baumannii.

Infections linked to Acinetobacter baumannii are one of the main risks of modern medicine. Biofilms formed by A. baumannii due to a protective extracellular polysaccharide matrix make them highly tolerant to conventional antibiotics and raise the possibility of antibiotic resistance. Antimicrobial peptides (AMPs) are gaining popularity due to their broad-spectrum actions and key properties of peptide self-assembly, making them a promising alternative to antibiotics. Here, we demonstrate that 12-residue synthetic self-assembled peptide SA4 nanostructures have enough antibacterial action to prevent the growth of mature bacterial biofilms. The SA4 peptide was successfully synthesized by using the solid-phase peptide synthesis method, and its self-assembly was prepared in water. The self-assembled peptide hydrogel formed nanotube structure was observed under a scanning electron microscope and further characterized to confirm their physical and molecular properties. The resulting hydrogel exhibits significant antibacterial activity against MDR A. baumannii strains (MDR-1 and MDR-2), responsible for many nosocomial infections. In addition, at various gel concentrations, this hydrogel has the potential to inhibit about 30-80% of biofilms formed by MDR strains. Furthermore, under a microscope, it has been observed that the rupture of the bacterial cell membrane and cell wall of A. baumannii cells is caused by peptide nanotubes generated by self-assemblies. Thus, peptide-based nanotubes present intriguing avenues for various biomedical applications. This is the first report of bacterial biofilm removal with SA4 peptide nanotubes, and offering a unique treatment for infections linked to biofilms.