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Project Title:  Evaluating the Spaceflight Infectious Disease Risk Potential of Pathogenic and Commensal microorganisms using Caenorhabditis elegans as a Human Surrogate Model for Infection Reduce
Fiscal Year: FY 2014 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
 Start Date: 09/09/2013  
End Date: 09/08/2014  
Task Last Updated: 12/07/2014 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Barrila, Jennifer  Ph.D. / Arizona State University 
Address:  Center for Infectious Diseases and Vaccinology 
1001 S McAllister Avenue 
Tempe , AZ 85287-0001 		 Email: Jennifer.Barrila@asu.edu 
Phone: 860-949-2423  
Congressional District: 9 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Arizona State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Castro, Sarah  NASA Johnson Space Center 
Project Information: Grant/Contract No. NNX13AR16G 
Responsible Center: NASA JSC 
Grant Monitor: Whitmore, Mihriban  
Center Contact: 281-244-1004 
mihriban.whitmore-1@nasa.gov 
Unique ID: 9452  		Solicitation / Funding Source: 2012 Crew Health NNJ12ZSA002N 
Grant/Contract No.: NNX13AR16G 
Project Type: Ground 
Flight Program:  
TechPort: No  		No. of Post Docs: 0 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 0  		No. of PhD Degrees: 0 
No. of Master's Degrees: 0 
No. of Bachelor's Degrees: 0 
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Medical Conditions:Risk of Adverse Health Outcomes and Decrements in Performance Due to Medical Conditions that occur in Mission, as well as Long Term Health Outcomes Due to Mission Exposures
(2) Microhost:Risk of Adverse Health Effects Due to Host-Microorganism Interactions
Human Research Program Gaps: (1) Medical-501:We need to develop integrated exploration medical system models for the Moon and Mars.
(2) Micro-101:Evaluate the effects of isolation, confinement and weightlessness on changes in the vehicle microbiome, the human microbiome, and microbial virulence.
(3) Micro-102:Evaluate whether deep-space radiation has an additive or synergistic effect with weightlessness/isolation/confinement on microbial types, numbers, and virulence.
(4) Micro-103:Evaluate whether atmospheric composition, such as elevated CO2 levels or mildly hypoxic exploration atmospheres, are a significant contributor to changes in the microbial profile of spaceflight.
(5) Micro-201:Micro-201: Evaluate the contribution of changes in microbial numbers, types, and virulence on the likelihood and consequence of adverse health events (infection), during the mission.
Task Description: Understanding the impact of the spaceflight environment on the disease-causing potential of a wide variety of pathogenic and commensal microbes is critical for ensuring crew health, safety, and performance. Changes that occur to both the immune system of astronauts and pathogenesis of microbes during spaceflight could represent a formidable challenge to the successful transition from short-to-long duration missions. This is a critical issue to address since a) the crew’s immune system is dysfunctional during flight, and b) results from our collaborative team and others have demonstrated that spaceflight and/or spaceflight-analogue culture globally alters the virulence, gene expression, and/or pathogenesis-related phenotypes of several microbial pathogens. This proposal aims to further improve infectious disease risk assessment for astronauts by investigating the likelihood that a variety of microorganisms may exhibit alterations in virulence in response to the microgravity environment. We will accomplish this by profiling changes in virulence, persistence in the host, and targeted changes in gene expression of a select panel of pathogenic and commensal microorganisms exposed to spaceflight-analogue culture using the Rotating Wall Vessel (RWV) bioreactor. Microbes proposed for this study include 1) Salmonella Typhimurium, 2) Staphylococcus aureus, 3) a Space Shuttle environmental isolate of Burkholderia cepacia, and 4) Lactobacillus acidophilus, a commensal microorganism. The nematode Caenorhabditis elegans (C. elegans) will be used as a human surrogate model of infection to evaluate changes in microbial virulence in response to RWV culture and will also be profiled for targeted changes in the expression of genes important for host immunity. Moreover, as astronauts have dysfunctional immune systems during spaceflight, the susceptibility of an immunocomprised C. elegans mutant to infection with these same microbes will also be evaluated. Results from this work hold potential to provide deeper insight into the likelihood, consequence, and respective uncertainties of this HRP risk.

Research Impact/Earth Benefits: This research will broaden our knowledge of the host-pathogen interaction that leads to infectious disease, and will provide fundamental new insight into mechanisms important for the development of new therapeutic strategies to combat infectious disease for the general public.

Task Progress & Bibliography Information FY2014 
Task Progress: Understanding the impact of the spaceflight environment on the virulence potential of a wide variety of microorganisms is critical for ensuring crew health, safety, and performance. Changes that occur to both the immune system of astronauts and pathogenesis of microbes during spaceflight could represent a formidable challenge to the successful transition from short-to-long duration missions. The goal of this work was to assess the feasibility of using the roundworm Caenorhabditis elegans (C. elegans) as a model host organism for investigating transient changes in virulence of microbes cultured under spaceflight analogue conditions in the Rotating Wall Vessel (RWV) bioreactor. The design of this study was such that only the bacteria were cultured in the RWV, while the C. elegans hosts (wild type and an immunocompromised mutant) were grown prior to infection on standard nematode growth media (NGM) agar plates on their normal laboratory diet of Escherichia coli OP50. The infections then took place in liquid medium using a variety of exposure times (1-18 hours) in order to minimize any reversion of the low-shear modeled microgravity (LSMMG)-associated phenotypes (i.e., changes in virulence and pathogenesis-related stress resistance) during the infection. Microorganisms profiled in this work included: 1) Salmonella enterica serovar Typhimurium, 2) Staphylococcus aureus, and 3) an ISS potable water isolate of Burkholderia cepacia.

Under the conditions of this study, we found that transient exposure of the RWV-cultured microbes to C. elegans in a static dish was not sufficient for establishing a lethal infection in the nematode relative to the uninfected control nematodes fed on OP50. The outcomes of the infection process in liquid were quite different from what was previously reported for these pathogens using a solid agar medium. This indicates the need for further study design optimization. Persistence studies with S. Typhimurium did however indicate an early difference in the bacterial colonization numbers within the nematode intestine infected with LSMMG versus control cultures. We also observed an interesting phenotype following S. aureus infection, in which the bacterium appeared to form a biofilm-like structure around the anterior of the worm in liquid. Studies are ongoing to further investigate these findings.

Bibliography: Description: (Last Updated: 12/08/2014) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Castro SL, Nickerson CA, Ott CM, Forsyth RJ, Rideout A, Alverdy JC, Barrila J. "Evaluating the Spaceflight Infectious Disease Risk Potential of Pathogenic and Commensal microorganisms using Caenorhabditis elegans as a Human Surrogate Model for Infection." Presented at the 2014 Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014.

2014 Human Research Program Investigators’ Workshop, Galveston, TX, February 12-13, 2014. Immunology and Microbiology Posters, http://www.hou.usra.edu/meetings/hrp2014/pdf/3267.pdf , Feb-2014

Abstracts for Journals and Proceedings Barrila J, Ott CM, Forsyth RJ, Davis R, Wilson JW, Nickerson CA. "Experimental Considerations for the Proper Assessment of Spaceflight-induced alterations in Microbial Virulence " 30th Annual Meeting of the American Society for Gravitational and Space Research, Pasadena, CA, October 22-26, 2014.

30th Annual Meeting of the American Society for Gravitational and Space Research, Pasadena, CA, October 22-26, 2014. Abstract number IP.32. , Oct-2014

Awards Barrila J. "2014 Thora W. Halstead Young Investigator's Award, American Society for Gravitational and Space Research, October 2014." Oct-2014
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Project Title:  Evaluating the Spaceflight Infectious Disease Risk Potential of Pathogenic and Commensal microorganisms using Caenorhabditis elegans as a Human Surrogate Model for Infection Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
 Start Date: 09/09/2013  
End Date: 09/08/2014  
Task Last Updated: 09/18/2013 		 Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Barrila, Jennifer  Ph.D. / Arizona State University 
Address:  Center for Infectious Diseases and Vaccinology 
1001 S McAllister Avenue 
Tempe , AZ 85287-0001 		 Email: Jennifer.Barrila@asu.edu 
Phone: 860-949-2423  
Congressional District: 9 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Arizona State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Castro, Sarah  LZ TECHNOLOGY, INC. 
Project Information: Grant/Contract No. NNX13AR16G 
Responsible Center: NASA JSC 
Grant Monitor: Whitmore, Mihriban  
Center Contact: 281-244-1004 
mihriban.whitmore-1@nasa.gov 
Unique ID: 9452  		Solicitation / Funding Source: 2012 Crew Health NNJ12ZSA002N 
Grant/Contract No.: NNX13AR16G 
Project Type: Ground 
Flight Program:  
TechPort: No  		No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:   		No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Medical Conditions:Risk of Adverse Health Outcomes and Decrements in Performance Due to Medical Conditions that occur in Mission, as well as Long Term Health Outcomes Due to Mission Exposures
(2) Microhost:Risk of Adverse Health Effects Due to Host-Microorganism Interactions
Human Research Program Gaps: (1) Medical-501:We need to develop integrated exploration medical system models for the Moon and Mars.
(2) Micro-101:Evaluate the effects of isolation, confinement and weightlessness on changes in the vehicle microbiome, the human microbiome, and microbial virulence.
(3) Micro-102:Evaluate whether deep-space radiation has an additive or synergistic effect with weightlessness/isolation/confinement on microbial types, numbers, and virulence.
(4) Micro-103:Evaluate whether atmospheric composition, such as elevated CO2 levels or mildly hypoxic exploration atmospheres, are a significant contributor to changes in the microbial profile of spaceflight.
(5) Micro-201:Micro-201: Evaluate the contribution of changes in microbial numbers, types, and virulence on the likelihood and consequence of adverse health events (infection), during the mission.
Task Description: Understanding the impact of the spaceflight environment on the disease-causing potential of a wide variety of pathogenic and commensal microbes is critical for ensuring crew health, safety and performance. Changes that occur to both the immune system of astronauts and pathogenesis of microbes during spaceflight could represent a formidable challenge to the successful transition from short-to-long duration missions. This is a critical issue to address since a) the crew’s immune system is dysfunctional during flight, and b) results from our collaborative team and others have demonstrated that spaceflight and/or spaceflight-analogue culture globally alters the virulence, gene expression and/or pathogenesis-related phenotypes of several microbial pathogens. This proposal aims to further to improve infectious disease risk assessment for astronauts by investigating the likelihood that a variety of microorganisms may exhibit alterations in virulence in response to the microgravity environment. We will accomplish this by profiling changes in virulence, persistence in the host, and targeted changes in gene expression of a select panel of pathogenic and commensal microorganisms exposed to spaceflight-analogue culture using the Rotating Wall Vessel (RWV) bioreactor. Microbes proposed for this study include 1) Salmonella Typhimurium, 2) Staphylococcus aureus, 3) a Space Shuttle environmental isolate of Burkholderia cepacia, and 4) Lactobacillus acidophilus, a commensal microorganism. The nematode Caenorhabditis elegans (C. elegans) will be used as a human surrogate model of infection to evaluate changes in microbial virulence in response to RWV culture and will also be profiled for targeted changes in the expression of genes important for host immunity. Moreover, as astronauts have dysfunctional immune systems during spaceflight, the susceptibility of an immunocomprised C. elegans mutant to infection with these same microbes will also be evaluated. Results from this work hold potential to provide deeper insight into the likelihood, consequence and respective uncertainties of this HRP risk.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2013 
Task Progress: New project for FY2013.

Bibliography: Description: (Last Updated: 12/08/2014) 

Show Cumulative Bibliography
 
 None in FY 2013
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