Project description:This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 454 genes compared to synchronous ground controls, which represented 8.4% of the analyzed ORFs. Spaceflight-cultured C. albicans induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to more normal bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in the actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, actin cytoskeleton, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed. This study represents an important basis for the assessment of the risk that commensal flora could play during spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.
Project description:This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 454 genes compared to synchronous ground controls, which represented 8.4% of the analyzed ORFs. Spaceflight-cultured C. albicans induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to more normal bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in the actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, actin cytoskeleton, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed. This study represents an important basis for the assessment of the risk that commensal flora could play during spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public. Cells were grown for 24 hours on the space shuttle or as ground-based controls, preserved in RNALater, and stored at -80C. Four samples of each flight- and ground-based controls were harvested for microarray analysis. GAP is Group Activation Pack and each GAP contains 8 FPAs. The numbers represent the # assigned to the particular GAP and the number assigned to the specific FPA (1-8) within the indicated GAP. The same hardware is used for the flight samples and the ground samples.
Project description:Background: Candida albicans is an opportunistic pathogenic yeast, which could become pathogenic in various stressful environmental factors including the spaceflight environment. In this study,we aim to explore the phenotypic changes and possible mechanisms of Candida albicans after exposure to spaceflight conditions. Results: The effect of Candida albicans after carried on the "SJ-10" satellite for 12 days was evaluated by proliferation, morphogenic, environmental resistance and virulence experiment. The result showed that the proliferation rate, biofilm formation, antioxidant capacity, cytotoxicity and filamentous morphology of Candida albicans were increased in the spaceflight group compared to the control group. Proteomics and metabolomics technology were used to analyze the profiles of proteins and metabolites in Candida albicans under spaceflight condition. Proteomic analysis identified 564 up-regulated proteins involved in ribosome, DNA replication, base excision repair and sulfur metabolism in spaceflight group. And 345 down-regulated proteins related to metabolic processes were observed. The metabolomic analysis found 5 different expressed metabolites. The combined analysis of proteomic and metabolomic revealed the accumulation of cysteine and methionine in Candida albicans after spaceflight. Conclusions: Mechanisms that could explain the results in phenotype experiment of Candida albicans were found through proteomic and metabolomic analysis. And our data provide an important basis for the assessment of the risk that Candida albicans could cause under spaceflight environment.
Project description:The study compared the protein composition of supraspinatus muscle from the spaceflight mice subjected to either the 13-day NASA STS-135 mission or the 30-day Bion-M1 mission and their corresponding ground control mice.
Project description:We perform microarray analysis of HUVECs upon stimulation with virulent wildtype C. albicans strain SC5314 or its efg1/efg1 cph1/cph1 hyphal-deficient derivative strain CAN34 to compare the gene expression profiles elicited from HUVECs in response to these strains. In addition, these responses are compared to that of TNF-alpha induced responses to determine which responses are Candida-specific. Keywords: comparison of host response to different Candida albicans morphologies
Project description:Purpose: To explore the influence of Candida albicans treatment in mice intestinal epithelia. Method: 108 CFU C. albicans or PBS was gavaged to Apoe-/- mice every 3 days for 2 weeks. mRNA profiles were generated by deep sequencing.Results: Several signaling pathways were changed after C. albicans treatment, including response to hypoxia pathway.