Abstract
The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as Pseudomonas aeruginosa, Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: “cell penetrating peptide + linker + amyloidogenic peptide”. We evaluated the antimicrobial effects of two peptides that were developed from sequences with different propensities for amyloid formation. Among the two hybrid peptides, one was found with antibacterial activity comparable to antibiotic gentamicin sulfate. Our peptides showed no toxicity to eukaryotic cells. In addition, we evaluated the effect on the antimicrobial properties of amino acid substitutions in the non-amyloidogenic region of peptides. We compared the results with data on the predicted secondary structure, hydrophobicity, and antimicrobial properties of the original and modified peptides. In conclusion, our study demonstrates the promise of hybrid peptides based on amyloidogenic regions of the ribosomal S1 protein for the development of new antimicrobial drugs against P. aeruginosa.
Highlights
The development of new antimicrobial peptides (AMPs) is an important area for bioengineering and biomedical applications [1,2,3]
New technologies have been demonstrated for the development of new antimicrobial peptides based on predicting candidate amino acid sequences in proteins, as implemented in Webservers as AmpGram [7], AMP Scanner [8], and CAMPR3 [9]
The task of developing new approaches to counteracting the spread of the pathogen is especially important for bacterial cells, such as P. aeruginosa, which play a role in the development of serious diseases and adaptively respond to many drugs, acquiring resistance to antibiotics [10,11,12,13]
Summary
The development of new antimicrobial peptides (AMPs) is an important area for bioengineering and biomedical applications [1,2,3]. The task of developing new approaches to counteracting the spread of the pathogen is especially important for bacterial cells, such as P. aeruginosa, which play a role in the development of serious diseases and adaptively respond to many drugs, acquiring resistance to antibiotics [10,11,12,13]. The adaptive resistance of P. aeruginosa includes biofilm formation as a diffusion barrier restricting the access of antibiotics to bacterial cells [15,16]. Current therapeutic options for the treatment of P. aeruginosa include the use of various combinations of antibiotics and the development of new antibiotics and antimicrobial peptides, as well as their combinations [19,20]. It has been shown that a wide range within efflux systems and mutations of P. aeruginosa strains evolutionarily increases the resistance of P. aeruginosa cells to antibiotics [24,25]
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