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An electronmicroscope study of the effect of sulphadiazine and trimethoprim on Enterobacter cloacae
R M Richards1, J Z Xing, D W Gregory
1School of Pharmacy, Robert Gordon University, Schoolhill, Aberdeen.
Abstract:
Electronmicroscopy of thin sections of log phase cells of Enterobacter cloacae NCTC 10005 grown for 4 h in the presence of sulphadiazine 250 micrograms/ml, trimethoprim 12.5 microliters/ml or the combination of sulphadiazine 250 micrograms/ml plus trimethoprim 12.5 micrograms/ml indicated that both agents caused marked morphological damage even though the MIC of sulphadiazine for the E. cloacae strain was > 3000 micrograms/ml. The damage took the form of electron-transparent areas devoid of ribosomes in the cytoplasm and detachment of the outer membrane. The latter was most marked with trimethoprim, which also caused damage to the cytoplasmic membrane. It is postulated that the synthesis of the peptidoglycan layer was affected by the antimetabolites since the morphological effects were strikingly similar to those caused by treatment of E. cloacae with disodium edetate plus lysozyme. Viable counts of cultures undergoing the same treatments as those prepared for electronmicroscopy indicated that although sulphadiazine merely partially inhibited growth it nevertheless enhanced the bactericidal action of trimethoprim over a 5-h period.
Insights
Sulfadiazine and trimethoprim cause significant cell damage in Enterobacter cloacae, even at sub-inhibitory concentrations. Combining these antibiotics enhances trimethoprim's bacterial killing effect.
Area of Science:
- Microbiology
- Bacterial cell structure
- Antimicrobial resistance
Background:
- Enterobacter cloacae is an opportunistic pathogen.
- Sulfadiazine and trimethoprim are antibiotics that target bacterial growth.
- Understanding the morphological effects of antibiotics is crucial for developing new treatments.
Purpose of the Study:
- To investigate the morphological damage caused by sulfadiazine and trimethoprim in Enterobacter cloacae.
- To determine the combined effect of these antibiotics on bacterial viability.
Main Methods:
- Electron microscopy was used to examine thin sections of Enterobacter cloacae cells.
- Cells were treated with sulfadiazine, trimethoprim, or a combination of both.
- Viable counts were performed to assess bacterial killing.
Main Results:
- Both sulfadiazine and trimethoprim induced significant morphological damage, including cytoplasmic alterations and outer membrane detachment.
- Trimethoprim caused more pronounced outer membrane damage and also affected the cytoplasmic membrane.
- The combination of antibiotics enhanced the bactericidal effect of trimethoprim.
Conclusions:
- Sulfadiazine and trimethoprim exhibit potent morphological disruptive effects on Enterobacter cloacae, suggesting interference with peptidoglycan synthesis.
- The combination therapy demonstrates synergistic antibacterial activity, enhancing the bactericidal efficacy of trimethoprim.