Resistance to fosfomycin

A second mechanism of acquired resistance to fosfomycin involves chromosomal mutations in sugar phosphate uptake pathways which are responsible for transporting fosfomycin into the cell. The alterations decrease accumulation of the antibiotic to levels below those required for inhibition. 

A-acetylglucosamine, providing the necessary carboxylate anchor for attachment of the pentapeptide required for bacterial peptidoglycan (cell wall) formation. Bacteria that encode a MurA orthologue where the susceptible Cys is replaced by an Asp (e.g., Mycobacteria) are intrinsically genetically resistant to fosfomycin (Fig. 1) (11, 12). 

B. Fosfomycin Fosfomycin is an anti metabolite inhibitor of cytosolic enolpyruvate transferase. This action prevents the formation of A-acetylmuramic acid, an essential precursor molecule for peptidoglycan chain formation. Resistance to fosfomycin occurs via decreased intracellular accumulation of the drug. 

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