## 4 Discussion
Interestingly, microarray studies published as part of the microgravity experiment conducted on STS-115 identified the upregulation of several genes associated with filamentous forms of the yeast, including _ALS1_, _ALS4_, _YTH1_, _SPT5_ and _STII_. Other genes associated with filamentation were either downregulated or unchanged, namely _ALS2_, _TEC1_ and _ALS2_[35]. Of particular interest, the expression of form-associated genes was consistent with the observed low level of filamentation, specifically the gene coding for hyphal wall protein (_HWP1_) was unchanged in flight samples (-1.09) and yeast wall protein (_YWP1_) was elevated in flight samples (2.1). Current and ongoing studies will contribute to a more comprehensive understanding of differential gene expression as related to _C. albicans_ cultivation in microgravity. One adaptation that has been fairly consistent among flight opportunities and in the HARV simulation experiments is an increased resistance of _C. albicans_ to AmB (Figure 8 and [31]). In spaceflight, the level of resistance is greater when cells grow to higher densities (FEP bags), although minimal dose dependence was observed in these same studies. It appears as though aqueous solutions of AmB are less stable than CAS, which may contribute to the difference in dose dependency observed between the Micro-6 (10 days of 4 \({}^{\circ}\)C storage following medium preparation) and the Micro-14/FEP (17 days of storage following medium preparation) experiments, although this loss of function was not predicted by pre-flight testing. A preliminary explanation is that AmB lost some efficacy during storage, resulting in drug levels that kept the growth of terrestrial samples in check, but had a milder impact on cells already observed to grow to a higher density in microgravity. The yeast susceptibility to CAS indicates that antifungal resistance is not broad spectrum and the difference between CAS and AmB may provide clues as to the molecular pathways that accompany the adaptation processes to microgravity. Specifically, we are evaluating the role of ergosterol in the adaptation process as it is described as being a cellular target for AmB cell association and pore formation [53]. Cell and colony morphology can be used as indicators as to the composition of the local environment since environmental stresses often lead to morphological transformations, including filamentation and colony extrusions [17]. As observed in Figure 7, cells from this study produced colonies with a spikey (or foot projection)-style colony morphology often associated with cells exposed to environmental stresses, such as increased levels of CO\({}_{2}\)[54; 8]. These studies suggest that cells cultivated in microgravity may produce and then respond to a microenvironment enriched in CO\({}_{2}\) and other waste products. Since both flight and terrestrial samples demonstrated the colony projections, it will be important to parse out the contributions of microgravity relative to the environment created within specific hardware. Indeed, whether different types of flight hardware modulate or mask the effects of microgravity is an important consideration in these and other spaceflight studies. There exists a limited, but useful inventory of spaceflight-compatible hardware within the industry, with more being developed continuously. Identifying features that are necessary for successful operations is important and potentially challenging. In the case of _C. albicans_, hardware choices were constrained by safety precautions related to potential virulence and by the metabolic gas production during growth. This gas production precluded the use of several hardware models because the integrity of individual compartments was routinely compromised by the internal pressure created by metabolic gas.