The uptake and intracellular accumulation of aminoglycoside antibiotics in lysosomes of cultured rat fibroblasts

P Tulkens, A Trouet - Biochemical Pharmacology, 1978 - Elsevier
P Tulkens, A Trouet
Biochemical Pharmacology, 1978Elsevier
The uptake and intracellular localization of aminoglycoside antibiotics: streptomycin,
dihydrostreptomycin, gentamicin, kanamycin and amikacin, has been studied in cultured rat
embryo fibroblasts, using cell fractionation techniques and microbiological assay. On a
volume basis, aminoglycosides are accumulated 2 to 5-fold by fibroblasts, over a wide range
of external concentrations. Accumulation proceeds slowly, and stable intracellular contents
of drugs are obtained only after 4 days of incubation. After differential or isopycnic …
Abstract
The uptake and intracellular localization of aminoglycoside antibiotics: streptomycin, dihydrostreptomycin, gentamicin, kanamycin and amikacin, has been studied in cultured rat embryo fibroblasts, using cell fractionation techniques and microbiological assay. On a volume basis, aminoglycosides are accumulated 2 to 5-fold by fibroblasts, over a wide range of external concentrations. Accumulation proceeds slowly, and stable intracellular contents of drugs are obtained only after 4 days of incubation. After differential or isopycnic centrifugation of cell homogenates, the antibiotics are found consistently associated with lysosomal acid hydrolases, and clearly dissociate from marker constituents of mitochondria, plasma membrane, endoplasmic reticulum or peroxisomes. This indicates that aminoglycosides enter cells, but are localized exclusively in lysosomes. We suggest that the relative inefficiency of aminoglycoside antibiotics to act against intracellular bacteria is due (1) to the acid pH prevailing in lysosomes, which depress the antibacterial activity of these drugs and defeat their accumulation in those organelles; (2) the lack of accumulation of these drugs in other subcellular structures, like phagosomes, which may harbour intracellular bacteria.
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