Fosfomycin kinase (FomA) and Fosfomycin monophosphate kinase (FomB) (FomA / FomB)

FomA and FomB are sequential kinases that provide resistance to the antibiotic fosfomycin by inactivating it through phosphorylation. FomA, a member of the amino acid kinase family, catalyzes the ATP-dependent phosphorylation of fosfomycin to fosfomycin monophosphate (FMP), while FomB further phosphorylates FMP to fosfomycin diphosphate (FDP). These enzymes were originally discovered in fosfomycin-producing organisms such as Streptomyces wedmorensis and Streptomyces fradiae, where they serve as a self-resistance mechanism to protect the producer from its own antibiotic. In these organisms, the phosphorylated forms of fosfomycin are unable to bind or inhibit the primary target, MurA, which is essential for peptidoglycan biosynthesis. While primarily found in biosynthetic clusters, these enzymes represent a significant mechanism of antibiotic resistance that can be transferred to or found in pathogenic bacteria like Pseudomonas species. Consequently, FomA and FomB are considered potential therapeutic targets for the development of adjuvant inhibitors designed to restore fosfomycin efficacy in resistant bacterial strains.

Other names

Fosfomycin resistance kinasesFomAFomBFosfomycin kinaseFosfomycin monophosphate kinase

FomA and FomB sequentially phosphorylate fosfomycin to inactive forms (fosfomycin monophosphate and fosfomycin diphosphate), preventing it from inhibiting the bacterial enzyme MurA.