DEVELOPMENT OF BROAD SPECTRUM ANTIMICROBIAL AGENTS; TARGETING THE CELL ENVELOPE BIOGENESIS PATHWAY OF GRAM-NEGATIVE; BACTERIAL PATHOGENS
The invention exploits a model of LPS biogenesis and the genes involved in that pathway, to test several small molecules in order to determine which ones would be most effective in bacterial growth inhibition. Moreover, this invention encompasses a unique technology by which they utilize luciferase genes fused with genes important in this pathway in order to measure (based upon expression of light) gene depletion (or accumulation).
Since its discovery more than 60 years ago, penicillin has been utilized to effectively treat a number of bacterial pathogens. However, disease-causing bacteria that have become resistant to antibiotic drug therapy are an increasing public health threat. Wound infections, burns, gonorrhea are just some of the diseases that have become resistant to current treatments. Roughly 70% of the bacteria that cause infections in hospitals are resistant to at least one of the drugs most commonly used for treatment.Pseudomonas aeruginosa, the microbe utilized in this invention, can be found on most surfaces including medical equipment and catheters. Moreover, this facultative anaerobe is known to infect the pulmonary and the urinary tract as well as wounds and burns.
Gram-negative bacteria have been shown to be resistant to antibiotics through a variety of pathways including low permeability of the bacterial cellular envelope and multidrug efflux pumps (pumps that actively pump toxins and small molecules from inside of the cells to the outside of the cell). Gram negative bacteria are also unique in that they express the lipopolysaccharide (LPS) on the outer membrane (OM).
Innovations and Advantages
The inventors have found a way to test entire libraries of compounds in order to find out whether they affect LPS biogenesis and ultimately in regulation of gram-negative bacterial growth.
The compounds that have been screened and found effective in blocking LPS formation could be considered for commercialization and development depending on functionality in humans and toxicity levels.
Selected compounds that were effective in blocking LPS formation in Pseudomonas Aeroginosa were further validated in E.Coli 0157H, Klebsiella Pneumoniae and Acenitobacter Baumanii.
This technology is available for exclusive or non-exclusive licensing globally.
For further information, please contact:
Michal Preminger, Director of Business Development
Reference Harvard Case #4068