The effect of fosfomycin on neutrophil function
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Published on: February 9, 2024
R Krause1, S Patruta, F Daxböck
1Division of Infectious Diseases, Department of Medicine, Karl-Franzens University Graz, Auenbruggerplatz 15, A-8036 Graz, Austria. robert.krause@kfunigraz.ac.at
Abstract:
Fosfomycin (cis-1,2-epoxypropyl phosphonic acid) is a cell wall synthesis-inhibiting antibiotic. We investigated the effect of fosfomycin on several indices of neutrophil function. Neutrophil phagocytosis was analysed by flow cytometry. Cytosolic calcium kinetics were assessed fluorometrically and neutrophil bactericidal ability was assessed by fluorescence microscopy. Intracellular reactive oxygen intermediate (ROI) production was analysed by flow cytometry and extracellular ROI by cytochrome c reductase assay. After fosfomycin incubation, phagocytosis was unaffected as assessed by the FACS assay. Fosfomycin incubation resulted in enhanced bactericidal ability, in increased intracellular calcium concentrations, elevated extracellular ROI production and decreased chemotaxis but it did not affect intracellular ROI production and chemokinesis.
Insights
Fosfomycin, an antibiotic, enhances neutrophil bactericidal ability and calcium signaling. However, it decreases neutrophil chemotaxis without impacting phagocytosis or intracellular reactive oxygen intermediate production.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Fosfomycin is a broad-spectrum antibiotic that inhibits bacterial cell wall synthesis.
- Neutrophils are critical immune cells involved in combating bacterial infections.
- Understanding antibiotic effects on neutrophil function is crucial for optimizing antimicrobial therapy.
Purpose of the Study:
- To investigate the impact of fosfomycin on key neutrophil functions.
- To assess how fosfomycin influences phagocytosis, bactericidal ability, calcium signaling, and reactive oxygen intermediate (ROI) production.
Main Methods:
- Neutrophil phagocytosis and intracellular ROI were analyzed using flow cytometry.
- Cytosolic calcium kinetics were measured fluorometrically.
- Bactericidal ability was assessed via fluorescence microscopy.
- Extracellular ROI production was determined using a cytochrome c reductase assay.
Main Results:
- Fosfomycin did not affect neutrophil phagocytosis.
- Enhanced neutrophil bactericidal ability was observed.
- Increased intracellular calcium concentrations and elevated extracellular ROI production were noted.
- Neutrophil chemotaxis was decreased, while chemokinesis and intracellular ROI production remained unaffected.
Conclusions:
- Fosfomycin modulates neutrophil function, enhancing bactericidal capacity and calcium signaling.
- The antibiotic's effect on chemotaxis warrants further investigation in the context of infection control.
- Fosfomycin may offer immunomodulatory benefits beyond its direct antimicrobial activity.
