[Pathogenecity of fosfomycin-resistant strains isolated from Escherichia coli].
Two fosfomycin-resistant strains, FRC14 (parent strain, Escherichia coli [E.coli] c73-18) and FRK104 (parent strain, E. coli O124), were isolated from spleens before the bacterial disappearance, after inoculating the parent strains intraperitoneally into mice and treating them with a single oral dose of fosfomycin. The resistant strains were successfully isolated by a replica method from a mass of sensitive cells of respective parent. To elucidate the pathogenesis of the resistant strains, their characteristics were investigated. The MIC of fosfomycin for FRC14 was 25 micrograms/ml (4 times the MIC for the parent) and that for FRK104 was 100 micrograms/ml (8 times the MIC for the parent). The strain FRC14 showed a defective utilization of sn-glycerol 3-phosphate (G3P), but utilization of other 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 utilization of G3P was recovered in the presence of cAMP. Thus, the strain FRK104 seemed to be a ptsI mutant. These resistant strains were diminished their killing activity for mice in comparison to that of the each parent strain when they were inoculated intraperitoneally. The cell number of FRC14 decreased or disappeared in blood and 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.
Kasai
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Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Tsuruoka
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000472:pathogenicity*; D005578:Fosfomycin / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014774:Virulence
D000900:Anti-Bacterial Agents; D005578:Fosfomycin