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Comparative pathogenicity of a wild-type strain and respiratory mutants of Candida albicans in mice
S Aoki1, S Ito-Kuwa, Y Nakamura
1General Research Institute, Nippon Dental University, Niigata, Japan.
Abstract:
The pathogenicity of a parent wild-type strain and three respiratory mutants of Candida albicans was examined in intravenously infected mice. The wild-type strain K grew well in the kidney and caused severe candidosis, and the 21-day LD50 value was 7.2 x 10(6) cells/mouse. A mutant with a low rate of respiration (KRD-8) whose growth rate in vitro was somewhat lower than that of the wild type, produced germ tubes in vitro to the same extent as the wild-type strain and was associated with mortality rates similar to those of the wild-type strain. Two respiration-deficient (petite) mutants (KRD-19 and KRD-51), whose growth rates in vitro were far lower than that of the wild-type strain, could neither colonize the kidney nor cause fatal infection, even at a dose of 10(8) cells/mouse. Formation of germ tubes and hyphal growth in vitro of the petite mutants were less extensive than those of the wild-type strain or KRD-8. Extracellular proteinase was produced at pH 3.5 by the wild-type strain and by KRD-8 but not by the petite mutants. From these results, it is most likely that the nonlethality of infection by the petite mutants in mice results primarily from the low capacity of growth of these mutants, even though the inability of the petite mutants to produce extracellular proteinase may be also related to some extent to their avirulence.
Insights
Respiratory deficient Candida albicans mutants showed reduced pathogenicity in mice. Petite mutants, with impaired growth and proteinase production, were avirulent, highlighting the importance of growth capacity in fungal infections.
Area of Science:
- Mycology
- Infectious Diseases
- Pathogenesis
Background:
- Candida albicans is an opportunistic fungal pathogen.
- Respiratory function is crucial for microbial virulence.
Purpose of the Study:
- To investigate the role of respiratory function in Candida albicans pathogenicity.
- To compare the virulence of wild-type and respiratory mutant strains in a murine model.
Main Methods:
- Intravenous infection of mice with wild-type and respiratory mutant strains of Candida albicans.
- Assessment of fungal growth, colonization, and mortality.
- In vitro analysis of growth rates, germ tube formation, and extracellular proteinase production.
Main Results:
- Wild-type Candida albicans caused severe candidosis with a 21-day LD50 of 7.2 x 10^6 cells/mouse.
- A low-respiration mutant (KRD-8) exhibited similar virulence to the wild-type.
- Respiration-deficient (petite) mutants (KRD-19, KRD-51) were non-lethal, unable to colonize kidneys, and showed reduced in vitro growth and proteinase production.
Conclusions:
- Impaired growth capacity is the primary factor contributing to the avirulence of petite Candida albicans mutants in mice.
- Reduced extracellular proteinase production may also play a role in the avirulence of these mutants.