Small molecule inhibitors of the fosfomycin resistance enzyme FosM from Mycobacterium abscessus

Skye Chiasson1, Tatum Smith1, Landon Bello1

  • 1Department of Chemistry & Biochemistry, The University of Alabama, 250 Hackberry Lane, Tuscaloosa, AL 35487, United States of America.

Insights

Fosfomycin is a broad-spectrum antibiotic hindered by resistance enzymes. Researchers tested existing inhibitors against Mycobacterium abscessus

Area of Science:

  • Microbiology
  • Drug Discovery
  • Biochemistry

Background:

  • Fosfomycin is a broad-spectrum antibiotic with potential clinical utility.
  • The emergence of fosfomycin-modifying enzymes limits its widespread use.
  • Mycobacterium abscessus is a challenging pathogen often requiring effective antibiotic treatment.

Purpose of the Study:

  • To evaluate previously identified inhibitors of Staphylococcus aureus FosB for their efficacy against FosM, the fosfomycin-modifying enzyme from Mycobacterium abscessus.
  • To lay the groundwork for future studies investigating FosM inhibition.

Main Methods:

  • Utilized compounds previously found to inhibit FosB from Staphylococcus aureus.
  • Tested these compounds for their inhibitory activity against the FosM enzyme from Mycobacterium abscessus.

Main Results:

  • The study successfully tested known FosB inhibitors against FosM.
  • Preliminary data suggests potential for these compounds in targeting FosM.

Conclusions:

  • Compounds that inhibit FosB may also inhibit FosM, offering a potential strategy against Mycobacterium abscessus.
  • Further detailed studies are warranted to explore the therapeutic potential of FosM inhibitors.