Genetic analysis of oxygen-sensitive mutants of Cryptococcus neoforman
s revealed two loci (oxy1 and oxy2) linking hyperoxia sensitivity to p
roduction of melanin, a known virulence factor. Hyperoxia-sensitive st
rain 562 (oxy1 oxy2) is albino and avirulent. oxy2-defective strains l
acking the oxy1 defect are melanin deficient but show normal hyperoxia
resistance. Mutants defective at three additional mapped melanin loci
fail to show hyperoxia sensitivity in the oxy1 background. Revertants
of strain 562, which regain the ability to synthesize melanin by muta
tion at suppressor sites unlinked to oxy2, retain the oxygen sensitivi
ty conferred by their oxy1 and oxy2 defects. These data identify the m
elanin gene oxy2 as unique in its association of hyperoxia resistance
and melanization.