Catecholamines and virulence of Cryptococcus neoformans.
Cryptococcus neoformans was unable to utilize catecholamines (epinephrine, norepinephrine, or dopamine) as sole carbon or nitrogen sources. Therefore, catecholamines are not essential growth factors for this fungus and the brain is not a preferred nutritional niche for its growth with regard to catecholamines. To establish whether the brain is a survival niche for C. neoformans and to explain the role of phenoloxidase as a virulence factor, a wild-type strain that had phenoloxidase activity and mutants which lacked it were exposed to an epinephrine oxidative system, and the survival of both strains was tested. The oxidative system contained epinephrine as an electron donor, Fe3+ as the catalytic transition metal ion, and hydrogen peroxide as an electron acceptor. The wild-type strain was found to be resistant to this oxidative system, whereas under the same conditions the mutant strain was susceptible and its survival decreased at a rate of 4 logs per h. Damage to high-molecular-weight DNA seems to be a causative factor of cell death after exposure of the mutants to the oxidative system. These results suggest that C. neoformans may survive in the brain because of its ability to utilize catecholamines for melanogenesis and thus neutralize the harmful effects of catecholamines which are manifested in the presence of hydrogen peroxide and transition metal ions. The role of phenoloxidase in resistance to the epinephrine oxidative system is also discussed.
Polacheck
I
I
Department of Clinical Microbiology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Platt
Y
Y
Aronovitch
J
J
D004156:Catechol Oxidase / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D003454:Cryptococcus / Q000472:pathogenicity*; D003455:Cryptococcus neoformans / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity*; D004271:DNA, Fungal / Q000187:drug effects; D004837:Epinephrine / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009154:Mutation; D010084:Oxidation-Reduction; D014774:Virulence
D002395:Catecholamines; D004271:DNA, Fungal; D005296:Ferrous Compounds; D008543:Melanins; D006861:Hydrogen Peroxide; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase; D004837:Epinephrine