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Pathogenicity of Saccharomyces cerevisiae in complement factor five-deficient mice
J K Byron1, K V Clemons, J H McCusker
1Department of Biology, Stanford University, California.
Abstract:
We have previously determined the relative virulence of isolates of Saccharomyces cerevisiae on the basis of differences in proliferation and resistance to clearance in CD-1 mice. These infections were not fatal. To further characterize S. cerevisiae pathogenesis, we studied a virulent clinical isolate, YJM128, and an avirulent nonclinical isolate, Y55, in C5-deficient mice. DBA/2N mice were infected intravenously with YJM128 or Y55, and temporal burdens of yeast cells in various organs 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 decreased 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 between days 2 and 7, whereas no mice infected with equivalent numbers of Y55 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 were most susceptible to infection with S. cerevisiae, with 63% infected 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 isolates were also more virulent in DBA/2N than CD-1 mice, causing > or = 40% mortality. These data indicate that C5 is a critical factor in host resistance against S. cerevisiae infections and further confirm the pathogenic potential of some isolates of S. cerevisiae.
Insights
Complement component 5 (C5) is critical for host resistance against Saccharomyces cerevisiae infections. C5-deficient mice showed increased susceptibility and mortality, highlighting C5
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Previous studies determined Saccharomyces cerevisiae isolate virulence using CD-1 mice, with non-fatal infections.
- Further characterization of S. cerevisiae pathogenesis is needed, particularly in immune-deficient models.
Purpose of the Study:
- To investigate the role of Complement component 5 (C5) in host resistance against S. cerevisiae infections.
- To compare the virulence of a clinical isolate (YJM128) and an avirulent isolate (Y55) in C5-deficient mice.
Main Methods:
- Intravenous infection of DBA/2N mice (C5-deficient) and C5-competent mice with S. cerevisiae isolates YJM128 and Y55.
- Quantification of yeast cell burdens in various organs over time.
- Mortality assessment in infected mice.
- Comparison of virulence between different mouse strains and S. cerevisiae isolates.
Main Results:
- In C5-deficient mice, the virulent isolate YJM128 caused significant mortality (90% with 10(7) CFU) and organ burden increases, especially in the brain and kidneys.
- The avirulent isolate Y55 did not cause mortality and showed decreased burdens in kidneys and brain.
- C5-deficient mice were significantly more susceptible to S. cerevisiae infection compared to C5-competent mice, with higher mortality and yeast burdens.
- Seven of ten other S. cerevisiae isolates demonstrated increased virulence in DBA/2N mice, causing at least 40% mortality.
Conclusions:
- Complement component 5 (C5) plays a critical role in host defense against S. cerevisiae infections.
- Certain S. cerevisiae isolates possess significant pathogenic potential, particularly in the context of compromised complement function.
- The C5-deficient mouse model is valuable for studying S. cerevisiae pathogenesis and host-pathogen interactions.