Ultrastructure and viability of K. pneumoniae treated with fosfomycin
Abstract:
The effect of Fosfomycin on K. pneumoniae ATCC 10031 was studied. The morphology on the electron microscopical level and the viability were markedly altered after application of 6 micrograms/ml and 60 micrograms/ml of Fosfomycin, respectively. These were chosen because they can be attained in man by oral or parenteral administration. Until 30 min after the administration of 6 micrograms/ml, and 10 min after administration of 60 micrograms/ml the turbidity increased in the same range as in the control. Thereafter the turbidity decreased but did not fall below its minimal values; after application of 6 micrograms/ml of Fosfomycin the OD remained at higher levels than after applying 60 micrograms/ml of Fosfomycin, at all corresponding times. The number of viable cells, after application of 6 micrograms/ml of Fosfomycin, was maximally reduced for 70% of the value at the time of administration. 60 micrograms/ml quickly impaired the ability of reproduction. Consequently, the CFU were reduced continuously, e.g. by 80% after 30 min and by more than 99% after 180 min. The finestructural alterations were characterized by loss of contrast and regular shape. The occurrence of protruded protoplasts and defects in the cell wall indicate the action of Fosfomycin on the bacterial envelope, preferably on the peptidoglycan layer.
Insights
Fosfomycin significantly alters Klebsiella pneumoniae morphology and viability. Even low doses impact bacterial cell walls, with higher concentrations rapidly inhibiting reproduction and reducing viable cell counts.
Area of Science:
- Microbiology
- Bacterial Physiology
- Antimicrobial Research
Background:
- Klebsiella pneumoniae is an opportunistic pathogen.
- Understanding antibiotic mechanisms is crucial for combating resistance.
- Fosfomycin is a broad-spectrum antibiotic.
Purpose of the Study:
- To investigate the effects of Fosfomycin on Klebsiella pneumoniae ATCC 10031.
- To analyze morphological and viability changes at the electron microscopic level.
- To correlate in vitro concentrations with potential human therapeutic levels.
Main Methods:
- Exposure of K. pneumoniae to Fosfomycin at 6 µg/ml and 60 µg/ml.
- Monitoring bacterial turbidity (optical density) over time.
- Quantifying viable cell counts (Colony Forming Units - CFU).
- Electron microscopy to observe ultrastructural changes.
Main Results:
- Fosfomycin induced significant morphological alterations, including loss of contrast and shape.
- Defects in the cell wall and protruded protoplasts were observed, suggesting peptidoglycan layer disruption.
- Bacterial turbidity initially increased then decreased, with higher ODs at lower Fosfomycin concentrations.
- Viability decreased by up to 70% with 6 µg/ml and rapidly impaired reproduction with 60 µg/ml, reducing CFU by over 99% within 180 minutes.
Conclusions:
- Fosfomycin effectively impacts K. pneumoniae morphology and viability.
- The antibiotic targets the bacterial envelope, likely the peptidoglycan layer.
- Observed effects support Fosfomycin's potential therapeutic efficacy against K. pneumoniae infections.
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