Repressor Proteins that Prevent Antibiotic Resistance in Certain Pathogenic Bacteria

Technology #14201

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Researchers
Kenneth M. Merz Jr.
Dhruva Chakravorty
Managed By
Lenny Terry
Assistant Director 352-392-8929
Patent Protection
US Patent 9,483,609

Aids in the Treatment of Staph and E-Coli Infections, Tuberculosis and Listeriosis

These repressor proteins combat antibiotic drug resistance in disease-causing bacteria, such as Staphylococcus aureus (staph), Mycobacterium tuberculosis, Listeria monocytogenes and Escherichia coli (e-coli) by interfering with metal ion homeostasis. Certain pathogenic bacteria contain specific proteins in the ArsR/SmtB family that confer antibiotic and heavy-metal resistance, making the bacteria difficult to eradicate from the human body. Researchers at the University of Florida have discovered metal ion sensing transcriptional repressor proteins that interfere with proteins in the ArsR/SmtB family. These proteins, which target ArsR/SmtB regulatory proteins, could halt antibiotic drug resistance and lead to the development of new pharmaceuticals that are safer for patients than available antibiotic cocktails. The demand for new tools to fight “superbugs” is high. Every year, antibiotic-resistant infections kill at least 20,000 Americans and cost the U.S. healthcare system an extra $20 billion.

Application

Proteins that interfere with pathogenic bacteria’s ability to resist heavy metals and antibiotics, which could lead to the development of new drug therapies and better molecular modeling by pharmaceutical companies

Advantages

  • Targets bacterial proteins without harming patients, creating safer treatment options for dangerous diseases
  • Opens the possibility of a new generation of antibiotics that overcome drug resistance, making it possible to effectively treat superbugs, including methicillin-resistant Staphylococcus aureus (MSRA)
  • Can be used with other bacterial proteins to treat disease, creating a new avenue for drug development

Technology

The ArsR/SmtB family of metal ion sensing transcriptional repressor proteins regulate the level of metal ions via metal ion homeostasis. Impairing this regulation in antibiotic-resistant pathogenic bacteria can weaken the organism, making it susceptible to antibiotics and the patient’s native immune system. These proteins share a fold that creates multiple pockets where drug molecules can dock, disrupting the protein’s conformational dynamics. This knowledge can be extended to other bacterial proteins with a similar fold pattern, opening up the possibility of new drug development. The scope of the invention also includes computer simulations and bioassays for identifying additional compounds that bind to regulatory proteins and impair allosteric reactions.