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Modified Antimicrobial Peptides For Enhanced Antibiotic Properties

Modified antimicrobial peptides with protein sequences for augmenting antimicrobial and antibiofilm properties.

Problem:

Antibiotic resistant bacteria are becoming more prevalent, while antibiotic innovation has slowed. Novel antimicrobial agents are needed to treat the 35,000 annual deaths from antibiotic resistant infections. While antimicrobial peptides (AMPs) have antibiotic potential, they lack potency to fight infections. The ability to modify AMPs and improve their antibiotic properties would result in a new generation of antimicrobial agents.

Solution:

The modified AMPs have robust antibiotic properties against lethal, drug resistant bacteria. The AMPs also disrupt biofilm formation when combined with low doses of common antibiotics.

Technology:

The inventors used computational modeling to determine the ideal pairing of AMP and activating protein sequence. The sequence is added to the AMP to improve its enzymatic activity. The modified AMPs have increased effectiveness against antibiotic resistant bacteria. The AMPs permeabilize bacterial membranes with reduced red blood cell toxicity. When combined with conventional antibiotics at low doses, the AMPs disrupted biofilm formation.

Advantages:

8-fold higher potency towards antibiotic resistant bacteria than original AMP
Effectively permeabilizes bacterial membranes
Reduced red blood cell toxicity
Decreases antibiotic concentration required to disrupt biofilm by 32-fold

Antimicrobial peptides (AMPs, light blue helix) are appended with activating protein sequences (ATCUN motifs, yellow, blue, and red). The modified AMPs have enhanced antimicrobial properties. When combined with common antibiotics, the AMPs also disrupt biofilms.