Effect of N-chlorotaurine on Aspergillus, with particular reference to destruction of secreted gliotoxin.
The fungistatic and fungicidal activity of N-chlorotaurine (NCT), a long-lived oxidant produced by stimulated neutrophils, was investigated. Physiological concentrations (75-100 microM) of NCT showed clear fungicidal activity against a range of Aspergillus isolates. Moreover, killing by NCT was significantly increased in the presence of ammonium chloride, explained by the formation of monochloramine by halogenation of ammonium. One clinical isolate of Aspergillus fumigatus was characterized for the production of the immunosuppressive agent gliotoxin, and NCT was shown to cause destruction of gliotoxin, possibly via reduction of the disulphide bridge. Because of its endogenous nature and its high antifungal activity, NCT appears to be a good choice for topical treatment of Aspergillus infections, and the results of this study further substantiate its therapeutic efficacy.
Reeves
Emer P
EP
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, NUI Maynooth, Co. Kildare, Ireland.
Nagl
Markus
M
Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
O'Keeffe
Joseph
J
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, NUI Maynooth, Co. Kildare, Ireland.
Kelly
Judy
J
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, NUI Maynooth, Co. Kildare, Ireland.
Kavanagh
Kevin
K
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, NUI Maynooth, Co. Kildare, Ireland.
D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism*; D005912:Gliotoxin / Q000378:metabolism*; D006801:Humans; D008826:Microbial Sensitivity Tests; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000935:Antifungal Agents; D000644:Quaternary Ammonium Compounds; D013654:Taurine; C043410:N-chlorotaurine; D005912:Gliotoxin