FosA

FosA refers to a family of bacterial enzymes that inactivate the antibiotic fosfomycin by catalyzing the conjugation of glutathione to the drug. These enzymes are typically cytosolic and Mn2+-dependent, though other divalent cations can sometimes support activity. The reaction opens fosfomycin’s epoxide ring, rendering the antibiotic unable to inhibit its target in the bacterial cell.

Genetics and variants: The fosA gene family includes multiple allelic variants such as fosA, fosA1, fosA2, fosA3, and others. Some variants are chromosomally encoded, while others are located on mobile genetic elements such as plasmids, which facilitates horizontal gene transfer between bacteria. Plasmid-borne variants like fosA3 have become widespread in Enterobacterales, including Escherichia coli and Klebsiella species, contributing to regional differences in fosfomycin resistance.

Clinical significance: FosA-mediated resistance is a major mechanism limiting the effectiveness of fosfomycin against Gram-negative pathogens. It often coexists with other resistance determinants on multidrug plasmids, complicating treatment options. The presence of fosA genes can influence local antibiotic resistance patterns and informs stewardship and surveillance efforts.

Detection and implications: Resistance can be assessed phenotypically via fosfomycin susceptibility testing, though the interpretation may vary by method. Molecular methods and sequencing can identify specific fosA alleles and track their spread. Understanding fosA distribution helps guide empirical therapy and infection-control strategies in settings with high rates of fosfomycin resistance.