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[Pathogenecity of fosfomycin-resistant strains isolated from Escherichia coli]
1Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Abstract:
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.
Insights
Fosfomycin-resistant Escherichia coli strains showed reduced virulence in animal models. These resistant strains, FRC14 and FRK104, exhibited impaired pathogenesis compared to their susceptible parent strains.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Antimicrobial Resistance
Background:
- Fosfomycin is a crucial antibiotic for treating bacterial infections.
- Emergence of antibiotic resistance poses a significant threat to public health.
- Understanding the characteristics of resistant bacterial strains is vital for developing effective treatment strategies.
Purpose of the Study:
- To investigate the pathogenesis and characteristics of two fosfomycin-resistant Escherichia coli strains, FRC14 and FRK104.
- To compare the virulence of these resistant strains with their susceptible parent strains in animal models.
Main Methods:
- Isolation of fosfomycin-resistant strains (FRC14 and FRK104) from infected mice using a replica method.
- Determination of fosfomycin Minimum Inhibitory Concentration (MIC) for resistant and parent strains.
- Characterization of carbohydrate utilization and identification of potential mutations (e.g., glpT, ptsI).
- Assessment of virulence by inoculating resistant and parent strains into mice and guinea pigs.
Main Results:
- Fosfomycin-resistant strains FRC14 and FRK104 exhibited significantly higher MIC values compared to parent strains.
- FRC14 demonstrated defective sn-glycerol 3-phosphate (G3P) utilization, suggesting a glpT mutation.
- FRK104 showed impaired carbohydrate utilization, with G3P utilization restored by cAMP, indicating a ptsI mutation.
- Both resistant strains displayed diminished killing activity in mice and reduced ability to cause keratoconjunctivitis in guinea pigs compared to parent strains.
Conclusions:
- Fosfomycin resistance in E. coli can be associated with mutations affecting nutrient utilization.
- The identified resistant strains (FRC14 and FRK104) exhibit reduced virulence and impaired pathogenesis.
- These findings highlight a potential trade-off between antibiotic resistance and bacterial fitness/virulence.