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[Uptake and intraphagocytic activity of teicoplanin in human neutrophils]
A B Rodríguez1, E Ortega, C Barriga
1Departamento de Fisiología, Facultad de Ciencias, Universidad de Extremadura, Badajoz, España.
Abstract:
The incorporation of antibiotics in phagocytes is necessary for their activity against intracellular microorganisms. The ability of Teicoplanin to enter in human polymorphonuclear leukocytes (PMNs) after infection with Candida albicans was investigated using an in vitro model previously described. Human PMNs were preincubated with Candida albicans for 30 min, after which antibiotic (100 mg/l) was added to cell suspension during 1, 5, 15, 30 and 60 min. The results were expressed as the ratio of the cellular concentration of antibiotic to the extracellular concentration (C/E). Teicoplanin bound rapidly to phagocytes (with a C/E = 2.12 after 1 min of incubation), being the cell-associated drug approximately similar during the entire incubation period. At the same time, Teicoplanin increases the percentage of mortality of Candida albicans previously ingested, which was dependent of the incubation period in its presence.
Insights
Teicoplanin rapidly enters human polymorphonuclear leukocytes (PMNs) and enhances their ability to kill ingested Candida albicans. This antibiotic uptake is crucial for effective phagocyte activity against intracellular fungal infections.
Area of Science:
- Pharmacology
- Immunology
- Mycology
Background:
- Antibiotic incorporation into phagocytes is essential for combating intracellular microorganisms.
- Polymorphonuclear leukocytes (PMNs) play a critical role in host defense against fungal pathogens like Candida albicans.
Purpose of the Study:
- To investigate the cellular uptake of Teicoplanin by human PMNs.
- To determine the impact of Teicoplanin on the mortality of Candida albicans ingested by PMNs.
Main Methods:
- An in vitro model was utilized involving human PMNs infected with Candida albicans.
- PMNs were incubated with Teicoplanin at various time points (1-60 min) to measure antibiotic concentration.
- The cellular to extracellular concentration ratio (C/E) of Teicoplanin was calculated.
Main Results:
- Teicoplanin demonstrated rapid uptake by PMNs, with a C/E ratio of 2.12 after 1 minute.
- Cell-associated Teicoplanin levels remained relatively constant throughout the incubation period.
- Teicoplanin significantly increased the mortality rate of ingested Candida albicans in a time-dependent manner.
Conclusions:
- Teicoplanin effectively penetrates human PMNs.
- The enhanced killing of Candida albicans by Teicoplanin-loaded PMNs suggests a potential therapeutic benefit against intracellular fungal infections.