Introduction: The rise of antibiotic-resistant bacteria worldwide has spurred the need for new treatment approaches. Antimicrobial Peptides (AMPs) are promising alternatives because of their broad-spectrum effects and novel action mechanisms. Among them, Amyloidogenic Antimicrobial Peptides (AAMPs) represent a novel approach that utilizes targeted coaggregation with essential bacterial proteins to disrupt cellular function. This study aimed to design and assess AAMPs that induce targeted coaggregation with bacterial ribosomal S1 protein, providing a potential alternative to traditional antibiotics. Method: Peptides were synthesized incorporating amyloidogenic sequences, TAT, and Antp fragments to enhance membrane penetration, and modified with non-standard amino acids for stability. ThT assays were performed in 50 mM Tris-HCl (pH 7.5) with 150 mM NaCl at 37°C. Antimicrobial efficacy was evaluated through growth inhibition assays on Staphylococcus aureus and Pseudomonas aeruginosa. MICs were determined via broth microdilution (two replicates). results: The synthesized AAMPs successfully induced the formation of fibrils in bacterial S1 ribosomal proteins, demonstrating their ability to coaggregate with target proteins. Incorporating TAT and Antp fragments enhanced the peptidesamp;amp;#039; ability to penetrate bacterial membranes, while the addition of non-standard amino acids, like sarcosine, improved their stability. Results: The synthesized AAMPs successfully induced the formation of fibrils in bacterial S1 ribosomal proteins, demonstrating their ability to coaggregate with target proteins. In vitro testing confirmed that these peptides exhibited antimicrobial activity by inhibiting the growth of S. aureus and P. aeruginosa. Discussion: This study demonstrates that AAMPs targeting bacterial ribosomal S1 proteins exhibit promising activity against pathogens such as S. aureus and P. aeruginosa. While these findings highlight the therapeutic potential of peptide-mediated coaggregation, further in vivo studies and safety assessments are required to evaluate their clinical applicability. Conclusion: This study highlights the potential of amyloidogenic antimicrobial peptides targeting bacterial S1 ribosomal proteins as a novel strategy to combat bacterial pathogens.
Galzitskaya et al. (Wed,) studied this question.