fosA1

fosA1 is a gene encoding a FosA-type glutathione S-transferase that confers resistance to the antibiotic fosfomycin in bacteria. It is one of several allelic variants of the fosA gene family, including fosA2 and fosA3. The encoded enzyme catalyzes the glutathione-dependent opening of the fosfomycin epoxide ring, thereby inactivating the drug. This reaction typically requires divalent metal ions such as Mn2+ or Mg2+ as cofactors. Expression of fosA1 in a susceptible host increases the minimum inhibitory concentration (MIC) of fosfomycin, reducing drug efficacy in vitro.

Genetic context for fosA1 can vary by species and strain, but fosA genes are frequently located on plasmids or other mobile genetic elements, enabling horizontal transfer between bacteria and contributing to the spread of resistance. Detection of fosA1 is usually accomplished by molecular methods such as PCR targeting fosA variants followed by sequencing, with phenotypic susceptibility testing providing supporting evidence of reduced fosfomycin activity.

Distribution reports indicate that fosA1 alleles have been identified in several Gram-negative bacteria, though the precise prevalence and species distribution depend on geographic and clinical context. Clinically, the presence of fosA1 can undermine fosfomycin-based treatment options, particularly in settings where compromised susceptibility limits the drug’s effectiveness. Surveillance and molecular characterization of fosA1 and related fosA variants continue to be important for understanding resistance patterns and guiding antimicrobial therapy.