FraB as a drug target and FraB inhibitors as Salmonella-specific narrow-spectrum therapeutics

& T2014-282 A method to discover narrow-spectrum antibiotics of salmonellosis, as well as small molecule inhibitors of Salmonella FraB and a Salmonella probiotic strain to enhance the efficacy of FraB inhibitors.

The Need

Non-typhoidal salmonellosis is one of the most significant food-borne diseases, in the United States and globally. There are no vaccines available for human use to prevent this disease, and only broad-spectrum antibiotics available to treat the disease. However, antibiotic resistance is on the rise and novel therapeutics are needed.

The Technology

Researchers at The Ohio State University, led by Dr. Brian Ahmer, discovered a Salmonella locus, whose mutation causes extreme attenuation of fitness in mice. This locus includes the Salmonella fraB gene and mutations in fraB cause an accumulation of the FraB substrate that is toxic to Salmonella. This led to an issued patent covering the method of selecting an agent that inhibits the expression or function of the fra locus of Salmonella, including inhibition of FraB.

Additionally, the inventors have discovered small molecule inhibitors of FraB through high-throughput screening using growth-based assays. 224,000 compounds were screened, and several compounds were found that inhibit Salmonella in a fra-dependent manner with IC50 values of 89-150 µM. Some were found to be uncompetitive inhibitors of FraB with Ki' values from 26-116 µM. Hit compounds are undergoing modification and further investigation.

A main benefit, this pathway is found in no animals and only a few bacteria, thus targeting FraB with novel antimicrobials is expected to leave the normal microbiota intact and have little or no effect on the host.

Commercial Applications

  • Salmonellosis therapeutics


  • Salmonella-specific narrow-spectrum treatment
  • Can limit the side effects caused by disruption of normal microbiota
  • Avoids selecting for microbial resistance among the normal microbiota
  • Can target Salmonella resistant to traditional antibiotics



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