Localization of azithromycin in Toxoplasma gondii-infected cells
- 1 July 1994
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 38 (7), 1620-1627
- https://doi.org/10.1128/aac.38.7.1620
Abstract
Agents effective against intracellular pathogens must enter infected cells, crossing vacuolar membranes surrounding the organisms and then penetrating into the microbe and localizing to the microbial target site. We have characterized these parameters for azithromycin entry into Toxoplasma gondii-infected Chinese hamster ovary cells and murine macrophage-like J774 cells. Azithromycin uptake into infected host cells was concentrative and was dependent upon proton gradients. Subcellular fractionation of azithromycin-loaded infected CHO cells demonstrated > 95% intracellular drug in host cell lysosomes and cytosol, with < 5% associated with the parasite. Uptake of azithromycin into the T. gondii vacuole increased if parasites were coated with antibody prior to internalization by murine J774 cells, conditions which result in the formation of acidified phagolysosomes. No redistribution or retention of azithromycin in the parasite was observed when drug efflux from antibiotic-loaded infected CHO cells was monitored. Azithromycin entry into extracellular T. gondii was concentrative, was temperature and pH dependent, and was not different when azithromycin-sensitive and -resistant parasites were compared. These results demonstrate that azithromycin concentrates primarily in acidified compartments in parasites and host cells. The high concentration of azithromycin within these compartments may not be biologically relevant to inhibition of intracellular parasite growth by this agent.Keywords
This publication has 34 references indexed in Scilit:
- Toxoplasmic Encephalitis in AIDSClinical Infectious Diseases, 1992
- Toxoplasma gondii : Fusion Competence of Parasitophorous Vacuoles in Fc Receptor-Transfected FibroblastsScience, 1990
- Antimicrobial Drugs, Microorganisms, and PhagocytesClinical Infectious Diseases, 1989
- Activity of A-56268 (TE-031), a new macrolide, against Toxoplasma gondii in miceJournal of Antimicrobial Chemotherapy, 1988
- In Vitro Assessment of Antimicrobial Agents Against Toxoplasma gondiiThe Journal of Infectious Diseases, 1988
- Effects of Extracellular Potassium on Acid Release and Motility Initiation in Toxoplasma gondiiThe Journal of Protozoology, 1987
- Phagosome acidification blocked by intracellular Toxoplasma gondiiNature, 1985
- Specific Labeling of Intracellular Toxoplasma gondii with Uracil*The Journal of Protozoology, 1977
- Toxoplasma gondii: Isolation and preliminary characterization of temperature-sensitive mutantsExperimental Parasitology, 1976
- Assessment in vitro of immunity against Toxoplasma gondii.The Journal of Experimental Medicine, 1975