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Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
Shorter Antibacterial Peptide Having High Selectivity for E. coli Membranes and Low Potential for Inducing Resistance
Adriana Barreto-Santamaría1,2, Zuly Jenny Rivera3, Javier Eduardo García4
1Receptor-Ligand Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50#26-20, Bogotá 111321, Colombia.
Abstract:
Antimicrobial peptides (AMPs) have been recognised as a significant therapeutic option for mitigating resistant microbial infections. It has been found recently that Plasmodium falciparum-derived, 20 residue long, peptide 35409 had antibacterial and haemolytic activity, making it an AMP having reduced selectivity, and suggesting that it should be studied more extensively for obtaining new AMPs having activity solely targeting the bacterial membrane. Peptide 35409 was thus used as template for producing short synthetic peptides (<20 residues long) and evaluating their biological activity and relevant physicochemical characteristics for therapeutic use. Four of the sixteen short peptides evaluated here had activity against E. coli without any associated haemolytic effects. The 35409-1 derivative (17 residues long) had the best therapeutic characteristics as it had high selectivity for bacterial cells, stability in the presence of human sera, activity against E. coli multiresistant clinical isolates and was shorter than the original sequence. It had a powerful membranolytic effect and low potential for inducing resistance in bacteria. This peptide's characteristics highlighted its potential as an alternative for combating infection caused by E. coli multiresistant bacteria and/or for designing new AMPs.
Insights
Researchers developed short synthetic antimicrobial peptides (AMPs) targeting bacterial membranes. A derivative, 35409-1, shows potent activity against multidrug-resistant E. coli with high selectivity and no hemolytic effects.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Antimicrobial peptides (AMPs) are crucial for combating resistant microbial infections.
- A Plasmodium falciparum-derived peptide (35409) showed antibacterial and hemolytic activity, indicating a need for improved selectivity.
- Developing AMPs that target bacterial membranes specifically is a key therapeutic goal.
Purpose of the Study:
- To create and evaluate short synthetic peptides derived from peptide 35409.
- To identify novel AMPs with potent antibacterial activity and reduced hemolytic effects.
- To assess the therapeutic potential of these synthetic peptides against multidrug-resistant bacteria.
Main Methods:
- Synthesis of sixteen short peptides (<20 residues) based on the 35409 template.
- Evaluation of antibacterial activity against E. coli strains, including multidrug-resistant isolates.
- Assessment of hemolytic activity and physicochemical properties, including stability in human sera.
Main Results:
- Four synthetic peptides demonstrated activity against E. coli without hemolytic effects.
- Peptide 35409-1 (17 residues) exhibited high selectivity for bacterial cells and stability in human sera.
- 35409-1 showed potent membranolytic activity, low resistance induction potential, and effectiveness against multidrug-resistant E. coli.
Conclusions:
- Peptide 35409-1 possesses promising therapeutic characteristics for combating E. coli infections.
- This peptide serves as a potential alternative to existing antibiotics against multidrug-resistant bacteria.
- The findings support the design of new AMPs with enhanced bacterial membrane targeting capabilities.
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