FosAtype

FosAtype refers to a family of enzymes known as FosA-type glutathione S-transferases that confer resistance to the antibiotic fosfomycin. These enzymes are metal-dependent and catalyze the conjugation of the tripeptide glutathione to fosfomycin, leading to inactivation of the drug. The reaction typically requires a divalent metal ion, most often manganese, and results in opening of fosfomycin’s epoxide ring to form a nonfunctional adduct.

FosA-type enzymes are part of the broader glutathione S-transferase superfamily but are distinguished by their substrate specificity for fosfomycin and their metal-dependent mechanism. A range of allelic variants has been identified, including FosA, FosA2, FosA3, FosA4, and FosA5, among others. Many variants are located on mobile genetic elements such as plasmids, facilitating horizontal transfer among Gram-negative bacteria, while others occur chromosomally in environmental or clinical isolates. The distribution of FosA alleles has been documented in species such as Klebsiella, Escherichia coli, and Pseudomonas, contributing to the global issue of fosfomycin resistance.

Clinical significance of FosAtype enzymes lies in their impact on treatment options. Fosfomycin is used for certain urinary tract infections and other infections caused by susceptible organisms; the presence of FosA-type enzymes can reduce or abolish the drug’s effectiveness, often alongside other resistance determinants. This has implications for antimicrobial stewardship, infection control, and susceptibility testing.

Detection typically involves molecular methods that target fosA genes, complemented by phenotypic assays to confirm fosfomycin resistance. Ongoing surveillance and research focus on understanding the evolution, spread, and inhibition of FosA-type enzymes.