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Updated: May 12, 2026

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
Correlation between pathogenicity and temperature sensitivity in different strains of Histoplasma capsulatum
Abstract:
We compared the mycelial to yeast transitions of the Downs strain of Histoplasma capsulatum (low level of virulence) with those of G184A and G222B, two more virulent strains having different levels of pathogenicity for mice. When the morphological transitions are initiated by a temperature shift from 25 degrees to 37 degrees C, all three strains undergo similar physiological changes, but these are less severe in G184A and G222B than in the Downs strain. The transitions from mycelial to yeast morphology in both of the more virulent strains are also one-third more rapid than in Downs. We also find that the differences in temperature sensitivity of the three strains can be correlated with the temperature required for complete uncoupling of oxidative phosphorylation. The differences in sensitivity to elevated temperatures extend to the growth of yeast cells of all three strains. Considered together, our results suggest that sensitivity to elevated temperatures may be a key factor accounting for differences in virulence and that uncoupling of oxidative phosphorylation may be the primary event in the morphological transition in all three strains.
Insights
Virulence differences in Histoplasma capsulatum strains correlate with temperature sensitivity. Elevated temperatures trigger rapid mycelial-to-yeast transitions, linked to oxidative phosphorylation uncoupling, impacting pathogenicity.
Area of Science:
- Mycology
- Pathogen Biology
- Cellular Physiology
Background:
- Histoplasma capsulatum exhibits morphological transitions crucial for its lifecycle and virulence.
- Different strains of H. capsulatum display varying levels of pathogenicity in mammalian hosts.
- Understanding the factors governing these transitions is key to controlling fungal infections.
Purpose of the Study:
- To compare the mycelial-to-yeast morphological transitions of H. capsulatum strains with differing virulence.
- To investigate the role of temperature sensitivity and oxidative phosphorylation in these transitions.
- To correlate physiological changes with observed differences in pathogenicity.
Main Methods:
- Comparative analysis of three H. capsulatum strains (Downs, G184A, G222B) with distinct virulence levels.
- Induction of morphological transition via a temperature shift from 25°C to 37°C.
- Assessment of physiological changes, transition speed, temperature sensitivity, and oxidative phosphorylation uncoupling.
Main Results:
- All strains exhibited physiological changes during temperature-induced transition, with less severe changes in more virulent strains (G184A, G222B).
- The more virulent strains showed a one-third faster mycelial-to-yeast transition compared to the Downs strain.
- Temperature sensitivity differences correlated with the temperature for oxidative phosphorylation uncoupling, affecting yeast cell growth.
Conclusions:
- Sensitivity to elevated temperatures is a potential key factor in H. capsulatum virulence.
- Uncoupling of oxidative phosphorylation appears to be the primary event driving the mycelial-to-yeast morphological transition.
- These findings offer insights into fungal pathogenesis and host-pathogen interactions.
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