Investigation of Host-Pathogen Interactions, Conserved Cellular Responses, and Countermeasure Efficacy During Spaceflight using the Human Surrogate Model Caenorhabditis elegans (NNX10AO52G)
Changes that occur to both the host immune system and pathogenesis of microbes during spaceflight represent a formidable challenge to the successful transition from short-to-long-duration spaceflight. While spaceflight has been shown to induce changes that can independently affect the host or the pathogen in a manner that is directly relevant to the development of infectious disease during spaceflight – no studies have been reported when both the host and pathogen are simultaneously exposed to the spaceflight environment. We propose to challenge the human surrogate model Caenorhabditis elegans with S. typhimurium during spaceflight to study the role of the intestine in host-pathogen interactions in real-time, define virulence mechanisms, identify evolutionarily conserved responses, and test novel therapeutic strategies to prevent infectious disease. We hypothesize that the combination of a spaceflight-induced increase in virulence of the pathogen coupled with a blunted immune response of the host will result in a synergistic effect on the host-pathogen interaction such that the risk of infectious disease during spaceflight is exacerbated. We further propose that these responses represent evolutionarily conserved mechanisms at the level of both host and pathogen that are dependent on media ion composition, specifically the local concentration of phosphate.
++ -- View more
The Micro-5 experiment infects the human surrogate model C. elegans with S. typhimurium during space flight and follows the survival of the C. elegans roundworms on orbit, compared to controls on Earth. Inflight infection of the whole C. elegans organisms will be accomplished by injecting bacterial growth on orbit. The use of phosphate as a nutritional countermeasure to protect C. elegans against infection with a foodborne pathogen will also be evaluated. Physiological data will be collected by video and RNA analysis.
Completed RNA-Seq gene expression profiles for C. elegans spaceflight and ground control cultures infected with Salmonella cultured in either Lennox Broth (LB) or LBM9 media (as well as flight and ground non-pathogenic E. coli controls cultured in the same media). RNA-Seq analysis was successfully performed (for both host and microbe) using high integrity RNA extracted from samples. Our findings indicate significant differences in gene expression between flight and ground samples.
Omics data is available from GeneLab's Data Repository at https://genelab-data.ndc.nasa.gov/genelab/