Product of fosC, a gene from Pseudomonas syringae, mediates fosfomycin resistance by using ATP as cosubstrate

Abstract

Pseudomonas syringe PB-5123, a producer of fosfomycin, is resistant to high concentrations of the antibiotic. Two possible mechanisms of resistance have been detected: (i) impermeability to exogenous fosfomycin, even in the presence of sugar phosphate uptake inducers, and (ii) antibiotic phosphorylation. The gene responsible for this last activity, fosC, encodes a ca. 19,000-Da protein and is immediately followed by a second open reading frame, which shows sequence similarities to glutathione S-transferases. FosC uses ATP as a cosubstrate in an inactivation reaction that can be reversed with alkaline phosphatase. Other nucleotide triphosphates cannot be substituted for ATP in this reaction. No relationship between fosC and the previously described genes of fosfomycin resistance was found.