Prevention and reversal of polymyxin drug resistance in gram negative bacteria

This technology is method to prevent or reverse polymyxin drug resistance in gram negative bacteria that can be used in combination with antibiotic therapies.

Unmet Need: Compounds to circumvent gram-negative bacterial defense against drug treatment

Current methods to treat antibiotic-resistant infections are limited by the rapid generation of resistant strains of bacteria and the limited discovery of drugs with alternate targets. Polymyxins are last resort antibiotics that have seen a recent revival to combat multidrug-resistant infections by gram-negative bacteria. However, resistance to this class of antibiotics can develop through active modification of lipid A, resulting in capping of the glucosamine sugar phosphates leading to the reduction of negative membrane charge. There are currently no drugs available for treating polymyxin-resistant bacterial infections.

The Technology: ArnT inhibition to prevent polymyxin resistance

This technology is a method for preventing polymyxin-class drug resistance by administering inhibitors or antagonists of aminoarabinose glycosyltransferase (ArnT). ArnT is a bacterial enzyme that attaches the positively charged aminoarabinose to the bacterial cell wall to reduce negative charge of the membrane and disrupt the binding of cationic polymyxin antibiotics. As a result, targeting ArnT with compounds to disrupt its function could provide a method for effectively eliminating or preventing polymyxin resistance. These inhibitors or antagonists targeting ArnT could be administered in combination with various antibacterial agents to increase the susceptibility of bacteria to treatment and prevent drug resistance.

Applications:

  • Prevention of polymyxin-class drug resistance in bacteria
  • Reversing antibiotic resistance in bacteria
  • Platform to screen molecules for inhibiting enzymatic activity critical to polymyxin drug resistance

Advantages:

  • Compatible with existing polymyxin antibiotic agents
  • Potential to identify multiple compounds through drug screening
  • Versatile method to design compounds against various bacterial strains

Lead Inventor:

Filippo Mancia, Ph.D.

Patent Information:

Patent Status

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