Abstract
Two fosfomycin-resistant strains, FRC 14 (parent strain, Escherichia coli [E.coli] c73-18) and FRK104 (parentstrain, E. coli 0124), were isolated from spleens before the bacterial disappearance, after inoculating the parentstrains intraperitoneally into mice and treating them with a single oral dose of fosfomycin. The resitant strainswere successfully isolated by a replica method from a mass of sensitive cells of respective parent. To elucidatethe pathogenesis of the resistant strains, their characteristics were investigated. The MIC of fosfomycin forFRC14 was 25μg/ml (4 times the MIC for the parent) and that for FRK 104 was 100 μg/ml (8 times the MIC forthe parent). The strain FRC14 showed a defective utilization of sn-glycerol 3-phosphate (G3P), but utilization ofother carbohydrates was similar to that of the parent strain. Thus, the strain FRC14 seemed to be a glpT mutant.The strain FRK104 did not use variety of carbohydrates including G3P, but used glucose 6-phosphate. The utilizationof G3P was recovered in the presence of cAMP. Thus, the strain FRK 104 seemed to be a ptsI mutant.These resistant strains were diminished their killing activity for mice in comparison to that of the each parentstrain when they were inoculated intraperitoneally. The cell number of FRC 14 decreased or disappeared in bloodand spleen in mice, while that of the parent increased. The strain FRK104 diminished its ability of producing keratoconjuctivitis in guinea pigs in comparison to that of the parent strain.
