The common yeast pathogen, Candida albicans, can cause a range of diseases from superficial skin infections to systemic and life threatening infections in immunocompromised individuals. Most members of the population are carriers of this yeast at some point in their lifetime. This point becomes more concerning for astronauts who experience diminished immune responsiveness during spaceflight. In addition, many bacteria have been shown to become more virulent when grown in space. The combination of increased virulence and diminished immunity can jeopardize the health and wellbeing of flight crew. The goal of these studies is to characterize the mechanisms underlying the adaptation responses we have observed in yeast grown in modeled microgravity and in spaceflight. In addition, we will focus on determining whether yeast also become more virulent when grown in space, as our observed cellular alterations might predict. Furthermore, we will define the environmental stressors that exist during spaceflight that influence yeast growth. Our overriding research goals are to characterize the virulence of Candida albicans in the space environment, to understand which aspects of the environment contribute to adaptive changes within the yeast, and to identify targets that might be exploited to control yeast infection in space and on Earth.
These studies described herein will further explore and document the genotypic and phenotype parameters of C. albicans associated with pathogenicity, identity specific environmental influences on the physiological adaptation processes, and provide insight into mechanisms used by higher eukaryotes when adapting to spaceflight conditions.
1. Evaluate the microgravity-induced alterations in biosynthetic regulation, cellular content, and subcellular localization of ergosterol and ß-glucans. (CMM-1a, 1b, 1d, OCB-3, P1, AH16)
2. Delineate the contributions of low fluid shear associated oxygen depletion and carbon dioxide enrichment in the microenvironment to cellular adaptation responses. (CMM-3, OCB-3, P1, AH16)
3. Characterize the effect of spaceflight on C. albicans virulence using a human monocyte host. (CMM-1d, CMM-4, P1)
For each sample, cell counts and cell morphology will be recorded. These embedded analyses, even when not the primary outcome measures for the experiment, will increase the dataset regarding spaceflight-associated cell growth and morphology while efficiently utilizing sample availability. Although opportunity will be limited to the control conditions for many of the experiments, we will make a concerted effort to obtain sufficient sample to perform microarray and metabolomics analyses (see Ergosterol section of first Aim).
This experiment is currently in progress. Results will be available at the conclusion of the study.