Amphotericin B enhances the synthesis and release of the immunosuppressive agent gliotoxin from the pulmonary pathogen Aspergillus fumigatus.
Exposure of the pulmonary pathogen Aspergillus fumigatus to amphotericin B alters membrane permeability as indicated by the escape of amino acids and protein from the mycelium. Amphotericin B exposure for periods of 2-4 h also leads to increased release of the immunosuppressive agent gliotoxin into the surrounding culture medium. Examination of the intracellular gliotoxin concentration following exposure to amphotericin B indicated elevated levels within the hyphae as well as in the culture medium--an effect which was also evident upon exposure of A. fumigatus to DMSO. These results indicate that in parallel with the ability of amphotericin B to act as a fungistatic agent it can also induce the synthesis of gliotoxin and facilitate its release by increasing the permeability of the fungal cell membrane. Increased synthesis of gliotoxin may result from the commencement of secondary metabolism in the presence of amphotericin B. The ability of amphotericin B to enhance the synthesis and release of gliotoxin may exacerbate the effects of the toxin and facilitate fungal invasion of pulmonary tissue.
Reeves
Emer P
EP
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, National University of Ireland Maynooth, Co. Kildare, Ireland.
Murphy
Thomas
T
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, National University of Ireland Maynooth, Co. Kildare, Ireland.
Daly
Paul
P
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, National University of Ireland Maynooth, Co. Kildare, Ireland.
Kavanagh
Kevin
K
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, National University of Ireland Maynooth, Co. Kildare, Ireland.
D000596:Amino Acids / Q000378:metabolism; D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003470:Culture Media; D003593:Cytoplasm / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism; D005912:Gliotoxin / Q000378:metabolism*; D025282:Mycelium / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D000935:Antifungal Agents; D003470:Culture Media; D005656:Fungal Proteins; D005912:Gliotoxin; D000666:Amphotericin B; D004121:Dimethyl Sulfoxide