Spaceflight and simulated microgravity conditions increase virulence of Serratia marcescens in the Drosophila melanogaster infection model
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ABSTRACT:
PROVIDER: PRJNA574643 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10197200_1.fastq.gz | Fastqsanger.gz | |||
| SRR10197200_2.fastq.gz | Fastqsanger.gz | |||
| SRR10197201_1.fastq.gz | Fastqsanger.gz | |||
| SRR10197201_2.fastq.gz | Fastqsanger.gz | |||
| SRR10197202_1.fastq.gz | Fastqsanger.gz |
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Project description:While it has been shown that astronauts suffer immune disorders after spaceflight, the underlying causes are still poorly understood and there are many variables to consider when investigating the immune system in a complex environment. Additionally, there is growing evidence that suggests that not only is the immune system being altered, but the pathogens that infect the host are significantly influenced by spaceflight and ground-based spaceflight conditions. In this study, we demonstrate that Serratia marcescens (strain Db11) was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but that the host immune system is not significantly altered amongst known immune genes. High-throughput sequencing of wild-type (w1118) adult hosts infected with either space or ground-reared S. marcescens revealed few changes in gene expression, with 11 genes significantly differentially expressed (q-values <0.05) and only one gene related to the immune system. This data supports the main findings of the paper, which state that both spaceflight and low-shear modeled microgravity conditions increase the virulence of this pathogen, independent of the host immune system. This data, which shows that there are no significant immune-related changes to the host when infected with space-grown sample compared to ground-grown sample, provides further evidence that there are likely phenotypic changes to the pathogen itself that is causing increased virulence in spaceflight and in low-shear modeled microgravity.
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Project description:While it has been shown that astronauts suffer immune disorders after spaceflight, the underlying causes are still poorly understood and there are many variables to consider when investigating the immune system in a complex environment. Additionally, there is growing evidence that suggests that not only is the immune system being altered, but the pathogens that infect the host are significantly influenced by spaceflight and ground-based spaceflight conditions. In this study, we demonstrate that Serratia marcescens (strain Db11) was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but the increased virulence phenotype of S. marcescens did not persist after the bacterial cultures were passaged on the ground. Increased virulence was also observed in bacteria that were grown in simulated microgravity conditions on the ground using the rotating wall vessel. Increased virulence of the space-flown bacteria was similar in magnitude between wild-type flies and those that were mutants for the well-characterized immune pathways Imd and Toll, suggesting that changes to the host immune system after infection are likely not a major factor contributing towards increased susceptibility of ground-reared flies infected with space-flown bacteria. Characterization of the bacteria shows that at later timepoints spaceflight bacteria grew at a greater rate than ground controls in vitro, and in the host. These results suggest complex physiological changes occurring in pathogenic bacteria in space environments, and there may be novel mechanisms mediating these physiological effects that need to be characterized.
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Project description:Microgravity is associated with immunological dysfunction, though the underlying mechanisms are poorly understood. Here, using single cell analysis of human peripheral blood mononuclear cells (PBMC)s exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways across immune cells under basal and stimulated states with a Toll like Receptor-7/8 agonist. At basal state, simulated microgravity altered the transcriptional landscape across immune cells, with monocyte subsets showing most pathway changes. Remarkably, short term simulated microgravity was sufficient to increase endogenous retroviral and mycobacterial transcripts. Under stimulation in simulated microgravity, nearly all immune cells demonstrated differences in functional pathways. Results from single cell analysis were validated against additional PBMC samples, including by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (i4) mission, JAXA6 mission, Twins study, and spleens from mice housed on the international space station. Combined results show significant impacts of microgravity on pathways essential for optimal immunity, including the cytoskeleton, interferon signaling, pyroptosis, temperature-shock, nuclear receptors, IL-6 signaling, HIF1α, and sirtuin signaling. Using machine learning, we identified numerous compounds linking microgravity to immune cell transcription, and demonstrate that the flavonol, quercetin, can reverse most abnormal pathways. These results offer insight into maladaptation of the immune system in microgravity, and provide opportunities to develop countermeasures that maintain normal immunity in space.
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Project description:Microgravity is one of the most important features in spaceflight. Previous evidence has shown that significant changes to the musculoskeletal and immune systems occurred under microgravity. The present study was undertaken to explore the change in protein abundance in human colon colorectal cells that were incubated for 48 or 72 h either in normal conditions and µG simulated conditions. The comparative proteomic method based on the 18O labeling technique was applied to investigate the up-regulated proteins and down-regulated proteins in SH-SY5Y under simulated microgravity.
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Project description:The below table includes a smaller list of data that was analyzed by dChip and filtered by pvalue such that a file with about 4600 genes was obtained, which allowed for ease of use from 40,000 genes. Keywords: static vs simulated microgravity
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