Method to Inhibit Antibiotic Resistance

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Researchers
Dr. Robert Shaw
Professor Shaw's research program involves the study of the structure and function of physiologically important metalloenzymes. Structures of the metal binding sites of these biological molecules are under investigation largely through the use of optical and electron paramagnetic resonance (EPR) spectroscopy. Mechanistic details of the functions of metal ions in these proteins are being studied through the use of spectroscopy coupled to rapid kinetic techniques in order to detect short-lived species such as reaction intermediates and enzyme complexes with substrates or inhibitors. Enzyme structure-function relationships are analyzed by site-directed mutagenesis combined with presteady-state spectroscopy and steady-state enzyme kinetic techniques.
External Link (www.depts.ttu.edu)
Patent Protection

Identifying nucleic acid ligand to lactamase; prevention and treatment of bacterial infections

US Patent US7772388 B2
Publications
Novel DNA and RNA inhibitors of metallo-ß-lactamase
The FASEB Journal, 2006
Antibiotic resistance in bacteria: novel metalloenzyme inhibitors.
NCBI, October 2009

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.


Market Applications:

• Pharmaceuticals

• 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


Development Stage:

Investigational patient trials have been conducted and in-vitro proof of concept has been completed.