TABLE 1.
Characteristics of fosfomycin-resistant E. coli mutants isolated in vitro
| Strain | Fosfomycin concn (mg/liter) used for isolationa | MIC (mg/liter)b
|
Growth on carbohydrates mM
|
Growthc
|
Resistance mutationd | Genes sequenced | |||
|---|---|---|---|---|---|---|---|---|---|
| With G6P | Without G6P | Without cAMP | With 1 mM cAMP | On α-GP | On G6P | ||||
| NU14 (parent) | 1 | 5 | + | + | + | + | |||
| DA6313 | 200 | 6 | >450 | − | −/+ | − | + | ptsI deletion | glpT |
| DA6326 | 500 | 6 | 900 | − | −/+ | − | + | ptsI deletion | gtpT |
| DA6396 | 50 + G6P | 12 | >1,000 | − | + | − | + | cyaA deletion | glpT, cyaA, uhpT, uhpA |
| DA6328 | 500 | 48 | 900 | + | + | − | + | glpT missense mutation | glpT |
| DA6400 | 50 + G6P | 48 | >1,000 | − | − | − | + | ND | glpT, cyaA, uhpT, uhpA |
| DA6399 | 50 + G6P | 128 | >1,000 | − | −/+ | − | − | cyaA insertion | uhpT, uhpA, cyaA |
| DA6395 | 50 + G6P | >1,024 | >1,000 | − | + | − | − | uhpT and cyaA nonsense mutation | glpT, cyaA, uhpT, uhpA |
| DA6398 | 50 + G6P | >1,024 | >1,000 | − | + | − | − | cyaA frameshift mutation | glpT, cyaA, uhpT, uhpA |
| DA6402 | 50 + G6P | >1,024 | >1,000 | − | + | − | − | cyaA insertion, uhpT deletion | glpT, cyaA, uhpA |
| DA6401 | 50 + G6P | >1,024 | >1,000 | − | − | − | − | uhpT missense mutation | glpT, cyaA, uhpT, uhpA |
| DA6393 | 50 + G6P | >1,024 | >1,000 | + | + | + | + | ND | glpT, cyaA, uhpT, uhpA |
| DA6394 | 50 + G6P | >1,024 | >1,000 | + | + | + | + | ND | glpT, uhpT |
| DA6397 | 50 + G6P | >1,024 | >1,000 | + | + | + | + | ND | glpT, uhpT, uhpA |
a
When included, the concentration of G6P was 50 mg/liter.
b
MIC determined by E-test with G6P or by streaking bacteria on LA plates with different concentrations of fosfomycin.
c
α-GP (used at 0.2%) is the preferred substrate of the GlpT transporter, and G6P (used at 0.2%) is the preferred substrate of the UhpT transporter system.
d
See Table 3 for details regarding type and site of mutations. ND, not determined.