Fosfomycin, sold under the brand name Monurol among others, is an antibiotic primarily used to treat lower urinary tract infections. Fosfomycin has broad antibacterial activity against both Gram-positive and Gram-negative pathogens, with useful activity against E. faecalis, E. coli, and various Gram-negatives such as Citrobacter and Proteus. Given a greater activity in a low-pH milieu, and predominant excretion in active form into the urine, fosfomycin has found use for the prophylaxis and treatment of infections caused by these pathogens. Activity against extended-spectrum β-lactamase-producing pathogens, notably ESBL-producing E. coli, is good to excellent, because the drug is not affected by cross-resistance issues. Existing clinical data support use in uncomplicated UTIs, caused by susceptible organisms. Development of bacterial resistance under therapy is a frequent occurrence and makes fosfomycin unsuitable for sustained therapy of severe infections. Three related fosfomycin resistance enzymes (named FosA, FosB, and FosX) are members of the glyoxalase superfamily. These enzymes function by nucleophilic attack on carbon 1 of fosfomycin, which opens the epoxide ring and renders the drug ineffective. Here you can see the high resolution structure of the dimeric Klebsiella pneumoniae fosfomycin-resistance protein (FosAKP) (PDB code: 8R37)

#molecularart ... #antibiotic ... #fosfomycin ... #resistance ... #klebeislla ... #xray

Structure rendered with @proteinimaging and depicted with @corelphotopaint