Two kinds of mutants defective in multiple carbohydrate utilization isolated from in vitro fosfomycin-resistant strains of Escherichia coli K--12.

Two types of in vitro fosfomycin-resistant mutants defective in multiple carbohydrate utilization were selected from Escherichia coli strain K--12. One mutant, FR182, was defective in phosphoenolpyruvate: sugar phosphotransferase system and the ability to form adenosine 3',5'-cyclic monophosphate (cAMP) was lowered. Another mutant, FR190, was defective in cAMP formation. Restoration by cAMP of fosfomycin (FOM) sensitivity coupled with recovery of utilization of many carbohydrates including sn-glycerol-3-phosphate (G-3-P) was observed in both of the resistant mutants. FOM was not taken up by these resistant strains but, in the cells cultured in the presence of cAMP, accumulation of FOM was equivalent to that of the sensitive parent strain. Decreased uptake of G-3-P was also restored in both of the resistant strains cultured in the presence of cAMP. These results indicate that the resistance to FOM in these mutants is due to impairment of G-3-P transport system, one of the pathways for uptake of FOM. They were sensitized to FOM by D-glucose-6-phosphate because of the induction of hexose phosphate transport system, another uptake pathway.