Due to the overuse of β-lactam antibiotics such as penicillin and cephalosporin in the clinical and agricultural fields, there has been a major increase in resistance to these antibiotics. This is a method if identifying a high affinity nucleic acid ligand to inhibit the activity of a lactamase enzyme, Metallo-B-Lactamase, which is a key player in antibiotic resistance. Targeting this molecule will allow the discontinuation of the catalytic hydrolysis reaction that destroys the antibiotic drug compound.
• Health Care/ Public Health.
• Biomedical Research
Features, Benefits & Advantages:
The most common cause of antibiotic resistance to Beta-lactam antibiotics comes from enzymes called Beta-lactamases. Beta-lactamases have the ability to catalyze the hydrolysis of the amide bonds in ?-lactam based antibiotics leaving them non-bactericidal. This is a method to identify the first clinically useful inhibitors.
Single stranded DNA’s which are potent inhibitors of the Bacillus cereus 5/B/6, have shown to the rapid, reversible, non-competitive inhibitors of this metalloenzyme. Microbiological growth experiments, using combinations of ssDNA with the b-lactam antibiotic cephalexin, reveal that the inhibitor is capable of causing cell death in liquid cultures of both Gram-positive and Gram-negative metallo-b-lactamase producing bacteria in the micromolar concentration range.
• Novel mechanisms of activity against multidrug-resistant pathogens.
• Use of aptamer inactivates metalloenzyme
• Potential for new pharmaceutical
Investigational patient trials have been conducted and in-vitro proof of concept has been completed.