PATHOGENICITY OF SACCHAROMYCES-CEREVISIAE IN COMPLEMENT FACTOR-5 DEFICIENT MICE

We have previously determined the relative virulence of isolates of Sa ccharomyces cerevisiae on the basis of differences in proliferation an d resistance to clearance in CD-1 mice. These infections were not fata l. To further characterize S. cerevisiae pathogenesis, we studied a vi rulent clinical isolate, YJM128, and an avirulent nonclinical isolate, Y55, in C5-deficient mice. DBA/2N mice were infected intravenously wi th YJM128 or Y55, and temporal burdens of yeast cells in various organ s were determined. After infection with 10(7) CFU, Y55 increased by 13 -fold and YJM128 increased by 20-fold in the brain from day 0 to 3. In addition, YJM128 increased by 4-fold in the kidneys, whereas Y55 decr eased by 16-fold. Both isolates declined in number in other organs. In all studies, 90% of mice infected with 10(7) CFU of YJM128 died betwe en days 2 and 7, whereas no mice infected with equivalent numbers of Y 55 died. No mice died after infection with 10(6) CFU of Y55 or YJM128. The importance of C5 was confirmed by studies using B10.D2/oSnJ (C5(- )) mice and their congenic C5(+) counterparts. Again, the C5(-) mice w ere most susceptible to infection with S. cerevisiae, with 63% infecte d with YJM128 dying by day 7; no C5(+) mice died. No Y55-infected mice died, and mean burdens in the brain at day 14 were sevenfold lower in C5(+) mice than in C5(-) mice. Seven of 10 other S. cerevisiae isolat es were also more virulent in DBA/2N than CD-1 mice, causing greater t han or equal to 40% mortality. These data indicate that C5 is a critic al factor in host resistance against S. cerevisiae infections and furt her confirm the pathogenic potential of some isolates of S. cerevisiae .