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Novel Compounds for the Potentiation of Antibiotic Resistance in Staphylococcus Aureus

Interests: Infectious Disease
Published:
Lead Inventor: Robert Daum
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SUMMARY

  • Currently there is no available vaccine for the prophylaxis of S. Aureus mediated infections such as MRSA, and antibiotics such as beta lactams and oxacillin are most commonly used for treatment. However, widespread and repeated use of these antibiotics is promoting treatment resistant infection.
  • The autoregulated VraSR operon is conserved among all S. Aureus strains and mediates a cell wall stress response implicated in antibiotic resistance. The inventors developed a reporter assay for VraSR-mediated transcription and screened the antimicrobial focused 13,840 member Life Chemicals library for inhibitors of VraSR. 
  • The invention is a novel therapeutic composition for treating antibiotic resistant S. Aureus infections (including MRSA) composed of a small molecule inhibitor of the VraSR operon, in combination with oxacillin. The combination treatment potentiates the sensitivity of MRSA to the antibiotic, thereby enabling the treatment of otherwise resistant strains.
  • In in vitro proof of concept experiments with the USA300 strain of MRSA, the most potent small molecule reduced the minimum inhibitory concentration (MIC) of oxacillin by over 4-fold.

 

FIGURE

In Vitro antibiotic kill assays with the USA300 strain of MRSA. Bacteria were cultured in the presense of oxacillin alone (red), the lead VraSA inhibitor alone (green), or the VraSA inhibitor in combination with oxacillin (blue). Results show the synergy between compound F1374-0037 and oxacillin. Parenthesis notes treatment concentration in ug/mL.

 

 

ADVANTAGES

ADVANTAGES

  • Can treat antibiotic resistant infections
  • Lowers concentration of antibiotics required for treatment
  • Panel of 4 lead compounds to chose from
  • Analogues synthesized
  • IP claims around both compositions and methods of treatment

 

APPLICATIONS

  • Treatment of antibiotic resistant S. Aureus infection (including MRSA) in:
  • Human Healthcare
  • Veterinary Healthcare
  • Drug Repurposing

 

PUBLICATIONS

 

 

 

 

 

 

  • US: 9,675,592
  • US Issued Patent: 9,861,616 (methods of use and composition claims)