Investigation of host-pathogen interactions conserved cellular responses and countermeasure efficacy during spaceflight using the human surrogate

Project: Research project

Project Details

Description

ABSTRACT 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-longduration spaceflight. This is a critical concern, since a) the immune system of the crew is dysfunctional during spaceflight, b) spaceflight uniquely increases the virulence and globally alters gene expression of the human pathogen Salmonella typhimurium when the bacteria are recovered post-flight and subsequently used to infect ground-based animal models, c) spaceflight-induced increases in S. typhimurium virulence are regulated by media ion composition, d) phosphate ion is sufficient to alter related pathogenesis responses in a groundbased spaceflight analogue model, and e) the evolutionarily conserved bacterial RNA chaperone protein, Hfq, serves as a master molecular regulator of many of these responses. 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 - none of these studies have been done when both the host and pathogen are simultaneously exposed to the spaceflight environment. To address this knowledge gap, 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.

Description

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. This is a critical concern, since a) the immune system of the crew is dysfunctional during spaceflight, b) spaceflight uniquely increases the virulence and globally alters gene expression of the human pathogen Salmonella typhimurium when the bacteria are recovered post-flight and subsequently used to infect ground-based animal models, c) spaceflight-induced increases in S. typhimurium virulence are regulated by media ion composition, d) phosphate ion is sufficient to alter related pathogenesis responses in a ground-based spaceflight analogue model, and e) the evolutionarily conserved bacterial RNA chaperone protein, Hfq, serves as a master molecular regulator of many of these responses. 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 - none of these studies have been done when both the host and pathogen are simultaneously exposed to the spaceflight environment. To address this knowledge gap, 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.
StatusFinished
Effective start/end date7/13/109/30/17

Funding

  • NASA: Ames Research Center: $1,183,167.00

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