Pathogenesis of Cryptococcus neoformans is associated with quantitative differences in multiple virulence factors

Two isolates of Cryptococcus neoformans were previously described as being highly divergent in their level of capsule synthesis in vivo and in their v irulence for mice. The highly virulent isolate (NU-2) produced more capsule than a weakly virulent isolate (184A) in vitro under tissue culture condit ions and in vivo. This investigation was done to determine if there were di fferences between the two isolates in other factors that might also contrib ute to virulence. Growth rate was not a factor as NU-2 grew more slowly tha n 184A. Based on PCR fingerprinting the two isolates were genetically diffe rent providing an opportunity to examine differences in multiple virulence traits. Quantitative analysis revealed that NU-2 expressed significantly mo re melanin and mannitol than did 184A. Although the isolates expressed the same capsular chemotype, NU-2 produced an additional structure reporter gro up (SRG) under tissue culture conditions that was not present when grown in glucose salts/urea/basal medium (GSU). Capsular polysaccharide SRGs of 184 A were unaffected by shifting the growth conditions from GSU to tissue cult ure conditions. Our results suggest that pathogenesis of a C. neoformans st rain is dictated by the quantitative expression of the strain's combined vi rulence traits. Regulators of the expression of these genes may be playing key roles in virulence.