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Published on: August 20, 2018
Enhancing the Antimicrobial Potency of Self-Assembling Antibiotics by Co-Assembly-Based Aggregation Modulation.
Bodhisattwa Das Gupta1, Rahul Kuiri1, Thangavel Vijayakanth2,3
1Department of Biotechnology, National Institute of Technology Durgapur, A-Zone, Mahatma Gandhi Road, Durgapur, West Bengal, India.
Modulating antimicrobial peptide (AMP) interactions enhances their potency. Co-assembling Fmoc-phenylalanine with Fmoc-glutamic acid broadens its antibacterial spectrum by disrupting bacterial membranes.
Area of Science:
- Biochemistry
- Materials Science
- Microbiology
Background:
- Antimicrobial peptides (AMPs) show promise as alternatives to conventional antibiotics.
- AMP activity is influenced by aggregation; weaker associations enhance function, while stable assemblies decrease it.
- Modulating intermolecular interactions is a potential strategy to boost AMP efficacy.
Purpose of the Study:
- To develop a general strategy for enhancing AMP potency.
- To broaden the activity spectrum of a Gram-positive-specific AMP, Fmoc-phenylalanine.
- To investigate the role of co-assembly with non-antibiotic peptides in modulating AMP function.
Main Methods:
- Co-assembly of Fmoc-phenylalanine with Fmoc-glutamic acid.
- Biophysical assays to assess membrane disruption and cell death.
- Rheological measurements to evaluate hydrogel mechanical rigidity.
- Molecular dynamics simulations to analyze fibril stability and interactions.
Main Results:
- Co-assembly broadened the activity spectrum of Fmoc-phenylalanine against Gram-positive bacteria.
- The co-assembled system effectively disrupted bacterial membrane integrity, causing cell death.
- Enhanced potency correlated with reduced hydrogel mechanical rigidity.
- Molecular dynamics simulations indicated that heterogeneous non-covalent interactions destabilized peptide fibrils.
Conclusions:
- Rationally designed co-assembling partners can weaken stabilizing non-covalent interactions.
- This weakening effect enhances the antibacterial efficacy of existing AMPs.
- Co-assembly presents a common strategy to improve AMP potency and broaden their spectrum of activity.
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