Naegleria fowleri: a free-living highly pathogenic amoeba contains trypanothione/trypanothione reductase and glutathione/glutathione reductase systems.
This paper presents definitive data showing that the thiol-bimane compound isolated and purified by HPLC from Naegleria fowleri trophozoites unequivocally corresponds by matrix assisted laser-desorption ionization-time-of-flight MS, to the characteristic monoprotonated ion of trypanothione-(bimane)(2) [M(+)H(+)] of m/z 1104.57 and to the trypanothione-(bimane) of m/z 914.46. The trypanothione disulfide T(S)(2) was also found to have a molecular ion of m/z 723.37. Additionally HPLC demonstrated that thiol-bimane compounds corresponding to cysteine and glutathione were present in Naegleria. The ion patterns of the thiol-bimane compounds prepared from commercial trypanothione standard, Entamoeba histolytica and Crithidia luciliae are identical to the Naegleria thiol-bimane compound. Partially purified extracts from N. fowleri showed the coexistence of glutathione and trypanothione reductases activities. There is not doubt that the thiol compound trypanothione, which was previously thought to occur only in Kinetoplastida, is also present in the human pathogens E. histolytica and N. fowleri, as well as in the non-pathogenic euglenozoan E. gracilis. The presence of the trypanothione/trypanothione reductase system in N. fowleri creates the possibility of using this enzyme as a new "drug target" for rationally designed drugs to eliminate the parasite, without affecting the human host.
Ondarza
Raúl N
RN
Center of Research on Infectious Diseases, National Institute of Public Health, Cuernavaca, Morelos, Mexico 62508, Mexico. ondarza@servidor.unam.mx <ondarza@servidor.unam.mx>
Hurtado
Gerardo
G
Tamayo
Elsa
E
Iturbe
Angélica
A
Hernández
Eva
E
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000302:isolation & purification / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000302:isolation & purification / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000302:isolation & purification* / Q000378:metabolism; D005980:Glutathione Reductase / Q000302:isolation & purification* / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000302:isolation & purification* / Q000378:metabolism; D016848:Naegleria fowleri / Q000201:enzymology / Q000378:metabolism* / Q000472:pathogenicity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013095:Spermidine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism; D014774:Virulence
D019086:Bridged Bicyclo Compounds, Heterocyclic; C021149:bimanes; C044809:trypanothione; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D005980:Glutathione Reductase; D005978:Glutathione; D003545:Cysteine; D013095:Spermidine