Relationship of Virulence Factor Expression to Evolved Virulence in

Serial passage of Cryptococcus neoformans in mice increases virulence relative to the nonpassaged line. Postpassaged lines showed no difference in the expression of most known virulence factors, with the exception that the more virulent lines had smaller capsules in vitro. These data imply that other mechanisms of virulence remain to be discovered. One approach to study the evolution of virulence experi-mentally is to serially passage a microbe in a host (8) and then compare the pre- and postpassaged lines to identify traits that affect changes in virulence. The yeast Cryptococcus neoformans is commonly found in the environment and causes disease primarily in immunocompromised humans. Its best-recognized virulence factors are the capsule (1, 14), melanin production (15, 25), laccase (17, 22), phospholipase (5), urease (6), and growth rate (18). Passage of C. neoformans in B10 major his-tocompatibility complex-congenic mice and BALB/c mice in-creased virulence relative to the nonpassaged line, using tim