RT Journal Article
T1 Molecular insights into fosfomycin resistance in Escherichia coli.
A1 Ballestero-Tellez, M
A1 Docobo-Perez, F
A1 Portillo-Calderon, I
A1 Rodriguez-Martinez, J M
A1 Racero, L
A1 Ramos-Guelfo, M S
A1 Blazquez, J
A1 Rodriguez-Baño, J
A1 Pascual, A
K1 Anti-Bacterial Agents
K1 Drug Resistance, Bacterial
K1 Genes, MDR
K1 Microbial Sensitivity Tests
AB Fosfomycin activity in  Escherichia coli  depends on several genes of unknown importance for fosfomycin resistance. The objective was to characterize the role of uhpT, glpT, cyaA and ptsI  genes in fosfomycin resistance in E. coli. Methods : WT E. coli BW25113 and null mutants, ΔuhpT, ΔglpT, ΔcyaA, ΔptsI, ΔglpT-uhpT, ΔglpT-cyaA, ΔglpT-ptsI, ΔuhpT-cyaA, ΔuhpT-ptsI and ΔptsI-cyaA, were studied. Susceptibility to fosfomycin was tested using CLSI guidelines. Fosfomycin mutant frequencies were determined at concentrations of 64 and 256 mg/L. Fosfomycin   in vitro  activity was tested using time –kill assays at concentrations of 64 and 307 mg/L ( human  Cmax).Results:  Fosfomycin MICs were: WT E. coli BW25113 (2 mg/L), ΔglpT (2 mg/L), ΔuhpT (64 mg/L), ΔcyaA (8 mg/L), ΔptsI (2 mg/L), ΔglpT-uhpT (256 mg/L), ΔglpT-cyaA (8 mg/L), ΔglpT-ptsI (2 mg/L), ΔuhpT-cyaA (512 mg/L), ΔuhpT-ptsI (64 mg/L) and ΔptsI-cyaA (32 mg/L). In the mutant frequency assays, no mutants were recovered from BW25113. Mutants appeared in ΔglpT, ΔuhpT, ΔcyaA and ΔptsI at 64 mg/L and in ΔuhpT and ΔcyaA at 256 mg/L. ΔglpT-ptsI, but not ΔglpT-cyaA, ΔuhpT-cyaA or ΔuhpT-ptsI, increased the mutant frequency compared with the highest frequency found in each single mutant. In time –kill assays, all mutants regrew at 64 mg/L. Initial bacterial reductions of 2–4 log10 cfu/mL were observed for all strains , except for ΔuhpT-ptsI, ΔglpT-uhpT and ΔuhpT-cyaA. Only ΔglpT and ΔptsI mutants were cleared using 307 mg/L.Conclusions:  Fosfomycin MIC may not be a good efficacy predictor, as highly resistant mutants may appear, depending on other pre-existing mutations with no impact on MIC.
PB Oxford University Press
YR 2017
FD 2017
LK http://hdl.handle.net/10668/10781
UL http://hdl.handle.net/10668/10781
LA en
NO Ballestero-Téllez M, Docobo-Pérez F, Portillo-Calderón I, Rodríguez-Martínez JM, Racero L, Ramos-Guelfo MS, et al. Molecular insights into fosfomycin resistance in Escherichia coli. J Antimicrob Chemother. 2017 May 1;72(5):1303-1309.
DS RISalud
RD Sep 7, 2025