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At least 19 records

Influence of Microgravity on Bacterial Pathogen Virulence and Immune Cell Function—Relevance for Infectious Disease Risk During Spaceflight

Spaceflight has measurable impacts on astronaut immune profiles as well as the virulence patterns of bacterial pathogens. Data with respect to human immunity indicate diminished T and NK cell function, altered cytokine profiles, persistent inflammation, and latent herpesvirus reactivation. Furthermore, evaluation of International Space Station (ISS) crewmembers gives evidence of compromised immunity, including atypical allergy, infectious disease, and dermatitis. Data with respect to certain human bacterial pathogens suggest modified virulence that may be enhanced. It is therefore critical to examine this interaction of immune dysregulation and increased microbial virulence and whether it might synergistically increase the risk of infectious disease to crew members. The goal of this study is to use modeled microgravity to study the impact of medically significant ISS bacteria that may have altered virulence on the immune response of the host. This study consists of two primary aims to assess this relationship. First, immune cells will be collected from healthy test subjects and cultured in static or in modeled microgravity conditions together with either control pathogens or with microgravity conditioned pathogens that were grown in bioreactors. Second, immune cells will be collected from astronauts before, during, and after flight and co-cultured with the control or the microgravity conditioned bacteria. Three pathogens were selected for this investigation: Pseudomonas aeruginosa , Salmonella enterica serovar Enteritidis and Burkholderia cepacia . Previously, the optimal cell to bacteria ratios that produce the greatest immune cell responses have been derived for these three bacteria. Cellular activation, as determined by the induction of cell surface activation markers and cytokine profiles, will be measured. Interactions between cells and bacteria will be assessed using fluorescent and electron microscopy techniques. This study will provide critical information to help understand how microgravity alters microbial virulence and the associated infectious disease risk to crewmembers during spaceflight missions. Over the past year, the Immunology and Microbiology laboratories at NASA Johnson Space Center have collaborated to process the astronaut subject samples to complete the last year of the flight portion of this study. This included the completion of four astronaut subjects full mission sampling sets. Sample processing included innate and adaptive cell flow cytometry as well as analysis of cytokine concentrations in the supernatant. The ground control segment of the study will take place during FY25 which involves parallel infections run under static and clinostat conditions. The acquired data sets over this 3-year study are now being analyzed to provide a comprehensive set of results and conclusions that will contribute to a more effective risk assessment for astronauts during spaceflight regarding this host-pathogen context.

Immunology↗

Microarray analysis identifies Salmonella genes belonging to the low-shear modeled microgravity regulon

The low-shear environment of optimized rotation suspension culture allows both eukaryotic and prokaryotic cells to assume physiologically relevant phenotypes that have led to significant advances in fundamental investigations of medical and biological importance. This culture environment has also been used to model microgravity for ground-based studies regarding the impact of space flight on eukaryotic and prokaryotic physiology. We have previously demonstrated that low-shear modeled microgravity (LSMMG) under optimized rotation suspension culture is a novel environmental signal that regulates the virulence, stress resistance, and protein expression levels of Salmonella enterica serovar Typhimurium. However, the mechanisms used by the cells of any species, including Salmonella, to sense and respond to LSMMG and identities of the genes involved are unknown. In this study, we used DNA microarrays to elucidate the global transcriptional response of Salmonella to LSMMG. When compared with identical growth conditions under normal gravity (1 x g), LSMMG differentially regulated the expression of 163 genes distributed throughout the chromosome, representing functionally diverse groups including transcriptional regulators, virulence factors, lipopolysaccharide biosynthetic enzymes, iron-utilization enzymes, and proteins of unknown function. Many of the LSMMG-regulated genes were organized in clusters or operons. The microarray results were further validated by RT-PCR and phenotypic analyses, and they indicate that the ferric uptake regulator is involved in the LSMMG response. The results provide important insight about the Salmonella LSMMG response and could provide clues for the functioning of known Salmonella virulence systems or the identification of uncharacterized bacterial virulence strategies.

Non-NASA Center↗

The Effect of Microgravity on the Smallest Space Travelers: Bacterial Physiology and Virulence on Earth and in Microgravity

Since the first human flights outside of Earth's gravity, crew health and well-being have been major concerns. Exposure to microgravity during spaceflight is known to affect the human immune response, possibly making the crew members more vulnerable to infectious disease. In addition, biological experiments previously flown in space have shown that bacteria grow faster in microgravity than they do on Earth. The ability of certain antibiotics to control bacterial infections may also differ greatly in microgravity. It is therefore critical to understand how spaceflight and microgravity affect bacterial virulence, which is their ability to cause disease. By utilizing spaceflight hardware provided by the European Space Agency (ESA), Dr. Barry Pyle and his team at Montana State University, Bozeman, will be performing an experiment to study the effects of microgravity on the virulence of a common soil and water bacterium, Pseudomonas aeruginosa. Importantly, these bacteria have been detected in the water supplies of previous Space Shuttle flights. The experiment will examine the effects of microgravity exposure on bacterial growth and on the bacterium's ability to form a toxin called Exotoxin A. Another goal is to evaluate the effects of microgravity on the physiology of the bacteria by analyzing their ability to respire (produce energy), by studying the condition of the plasma membrane surrounding the cell, and by determining if specific enzymes remain active. Proteins produced by the bacteria will also be assayed to see if the normal functions of the bacteria are affected. In the context of human life support in spaceflight, the results of this experiment will offer guidance in providing the highest possible water quality for the Shuttle in order to limit the risk of infection to human occupants and to minimize water system and spacecraft deterioration.

Pyle, Barry↗

Gene Expression of Pathogens in Simulated Microgravity

Extended exposure to radiation and microgravity in space has been linked to astronauts developing chronic diseases upon returning to Earth. The Gram-negative pathogen Serratia marcescens has been shown to potentially cause significant infections in humans and in insect models on Earth. Our recent findings also showed that S. marcescens shows an increase in virulence after a short period of growth in the spaceflight environment, which raises initiatives to find the correlation between space environment and the increased virulence. Because we know that the health of astronauts is immunocompromised in space, it is possible that the combination of increased bacterial virulence and the weakened immune system will cause astronauts to be more susceptible to chronic diseases in extended spaceflight. With 75% of human disease genes being conserved in the fruit fly Drosophila melanogaster, these insects act as an ideal model organism to study the human immune system. The high accessibility, low cost, high rate of reproductivity, and short lifespans of D. melanogaster facilitate efficient, high-quality research that seeks to understand altered virulence of this opportunistic pathogen. In this ground-based study, we will use a rotating wall vessel apparatus to simulate microgravity and determine how pathogenicity changes by evaluating differences in gene expression for S. marcescens between bacteria grown in simulated microgravity conditions and controls. We will compare the results of our findings to gene expression patterns in actual spaceflight samples of S. marcescens grown on the ISS (International Space Station) during a recent validation mission, to see if there are common mechanisms across our simulated microgravity and actual spaceflight microgravity samples that both show increased virulence in the fruit fly. With extended space travel in the foreseeable future, understanding how human physiology will be affected by these different factors will help mitigate risks and deaths.

spaceflight analogue↗

Differential partition of virulent Aeromonas salmonicida and attenuated derivatives possessing specific cell surface alterations in polymer aqueous-phase systems

Two-polymer aqueous-phase systems in which partitioning of biological matter between the phases occurs according to surface properties such as hydrophobicity, charge, and lipid composition are used to compare the surface properties of strains of the fish pathogen Aeromonas salmonicida. The differential ability of strains to produce a surface protein array crucial to their virulence, the A layer, and to produce smooth lipopolysaccharide is found to be important in the partitioning behavior of Aeromonas salmonicida. The presence of the A layer is shown to decrease the surface hydrophilicity of the pathogen, and to increase specifically its surface affinity for fatty acid esters of polyethylene glycol. The method has application to the analysis of surface properties crucial to bacterial virulence, and to the selection of strains and mutants with specific surface characteristics.

Van Alstine, J. M.↗

Low-shear modeled microgravity: a global environmental regulatory signal affecting bacterial gene expression, physiology, and pathogenesis

Bacteria inhabit an impressive variety of ecological niches and must adapt constantly to changing environmental conditions. While numerous environmental signals have been examined for their effect on bacteria, the effects of mechanical forces such as shear stress and gravity have only been investigated to a limited extent. However, several important studies have demonstrated a key role for the environmental signals of low shear and/or microgravity in the regulation of bacterial gene expression, physiology, and pathogenesis [Chem. Rec. 1 (2001) 333; Appl. Microbiol. Biotechnol. 54 (2000) 33; Appl. Environ. Microbiol. 63 (1997) 4090; J. Ind. Microbiol. 18 (1997) 22; Curr. Microbiol. 34(4) (1997) 199; Appl. Microbiol. Biotechnol. 56(3-4) (2001) 384; Infect Immun. 68(6) (2000) 3147; Cell 109(7) (2002) 913; Appl. Environ. Microbiol. 68(11) (2002) 5408; Proc. Natl. Acad. Sci. U. S. A. 99(21) (2002) 13807]. The response of bacteria to these environmental signals, which are similar to those encountered during prokaryotic life cycles, may provide insight into bacterial adaptations to physiologically relevant conditions. This review focuses on the current and potential future research trends aimed at understanding the effect of the mechanical forces of low shear and microgravity analogues on different bacterial parameters. In addition, this review also discusses the use of microgravity technology to generate physiologically relevant human tissue models for research in bacterial pathogenesis.

NASA Discipline Cell Biology↗

Spaceflight and Simulated Microgravity Increases Virulence of the Known Bacterial Pathogen S. Marcescens

After spaceflight, the number of immune cells is reduced in humans. In other research models, including Drosophila, not only is there a reduction in the number of plasmatocytes, but expression of immune-related genes is also changed after spaceflight. These observations suggest that the immune system is compromised after exposure to microgravity. It has also been reported that there is a change in virulence of some bacterial pathogens after spaceflight. We recently observed that samples of gram-negative S. marcescens retrieved from spaceflight is more virulent than ground controls, as determined by reduced survival and increased bacterial growth in the host. We were able to repeat this finding of increased virulence after exposure to simulated microgravity using the rotating wall vessel, a ground based analog to microgravity. With the ground and spaceflight samples, we looked at involvement of the Toll and Imd pathways in the Drosophila host in fighting infection by ground and spaceflight samples. We observed that Imd-pathway mutants were more susceptible to infection by the ground bacterial samples, which aligns with the known role of this pathway in fighting infections by gram-negative bacteria. When the Imd-pathway mutants were infected with the spaceflight sample, however, they exhibited the same susceptibility as seen with the ground control bacteria. Interestingly, all mutant flies show the same susceptibility to the spaceflight bacterial sample as do wild type flies. This suggests that neither humoral immunity pathway is effectively able to counter the increased pathogenicity of the space-flown S. marcescens bacteria.

immunity↗

Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

Wilson, J. W.↗

Low-Shear modeled microgravity alters the Salmonella enterica serovar typhimurium stress response in an RpoS-independent manner

We have previously demonstrated that low-shear modeled microgravity (low-shear MMG) serves to enhance the virulence of a bacterial pathogen, Salmonella enterica serovar Typhimurium. The Salmonella response to low-shear MMG involves a signaling pathway that we have termed the low-shear MMG stimulon, though the identities of the low-shear MMG stimulon genes and regulatory factors are not known. RpoS is the primary sigma factor required for the expression of genes that are induced upon exposure to different environmental-stress signals and is essential for virulence in mice. Since low-shear MMG induces a Salmonella acid stress response and enhances Salmonella virulence, we reasoned that RpoS would be a likely regulator of the Salmonella low-shear MMG response. Our results demonstrate that low-shear MMG provides cross-resistance to several environmental stresses in both wild-type and isogenic rpoS mutant strains. Growth under low-shear MMG decreased the generation time of both strains in minimal medium and increased the ability of both strains to survive in J774 macrophages. Using DNA microarray analysis, we found no evidence of induction of the RpoS regulon by low-shear MMG but did find that other genes were altered in expression under these conditions in both the wild-type and rpoS mutant strains. Our results indicate that, under the conditions of these studies, RpoS is not required for transmission of the signal that induces the low-shear MMG stimulon. Moreover, our studies also indicate that low-shear MMG can be added to a short list of growth conditions that can serve to preadapt an rpoS mutant for resistance to multiple environmental stresses.

Non-NASA Center↗

STS-107 Crew Interviews: William McCool, Pilot

STS-107 Pilot William McCool is seen during this preflight interview, where he gives a quick overview of the mission before answering questions about his inspiration to become an astronaut and his background. McCool outlines his role in the mission in general, and discusses the scientific experiments which comprise the primary payloads for the mission. He provides details on the following instruments and experiments: MEIDEX (Mediterranean Israeli Dust Experiment), BIOPACK (Bacterial Physiology and Virulence on Earth and in Microgravity) and SOLSE (Shuttle Ozone Limb Sounding Experiment). McCool talks about the new SPACEHAB research module which doubles the amount of space available for scientific research projects. He also mentions the training for the mission, the astronauts working in dual shifts on the shuttle, and the importance of international cooperation in planning the mission.

Source record↗

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

Non-NASA Center↗

Spaceflight Causes Increased Virulence of Serratia Marcescens on a Drosophila Melanogaster Host

Drosophila melanogaster, or the fruit fly, has long been an important organism for Earth-based research, and is now increasingly utilized as a model system to understand the biological effects of spaceflight. Studies in Drosophila melanogaster have shown altered immune responses in 3rd instar larvae and adult males following spaceflight, changes similar to those observed in astronauts. In addition, spaceflight has also been shown to affect bacterial physiology, as evidenced by studies describing altered virulence of Salmonella typhimurium following spaceflight and variation in biofilm growth patterns for the opportunistic pathogen Pseudomonas aeruginosa during flight. We recently sent Serratia marcescens Db11, a Drosophila pathogen and an opportunistic human pathogen, to the ISS on SpaceX-5 (Fruit Fly Lab-01). S. marcescens samples were stored at 4degC for 24 days on-orbit and then allowed to grow for 120 hours at ambient station temperature before being returned to Earth. Upon return, bacteria were isolated and preserved in 50% glycerol or RNAlater. Storage, growth, and isolation for ground control samples were performed using the same procedures. Spaceflight and ground samples stored in 50% glycerol were diluted and injected into 5-7-day-old ground-born adult D. melanogaster. Lethality was significantly greater in flies injected with the spaceflight samples compared to those injected with ground bacterial samples. These results indicate a shift in the virulence profile of the spaceflight S. marcescens Db11 and will be further assessed with molecular biological analyses. Our findings strengthen the conclusion that spaceflight impacts the virulence of bacterial pathogens on model host organisms such as the fruit fly. This research was supported by NASA's ISS Program Office (ISSPO) and Space Life and Physical Sciences Research and Applications (SLPSRA).

Serratia marcescens↗

Spaceflight-Induced Changes in Microbial Virulence and the Impact to the Host Immune Response

Many microbial pathogens have repeatedly exhibited unexpected responses relevant to infectious disease when grown in microgravity and microgravity analogue environments, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, host-pathogen interactions, and virulence. Notably, the classic foodborne pathogen Salmonella enterica serovar Typhimurium displayed increased virulence in animals when cultured in either the spaceflight analogue or true spaceflight environment. Recently, Serratia marcescens also was shown to increase virulence when cultured in the spaceflight environment. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system at multiple levels, which suggests an increased risk of infectious diseases. Moreover, astronauts have some degree of clinical infectious disease incidence. However, the contribution of the microgravity environment on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized. The goal of this study is to gain insight into the breadth of other medically significant microbial pathogens that may exhibit altered virulence and pathogenesis-related responses when cultured in spaceflight analogue conditions. Specifically, we are characterizing the effect of spaceflight analogue culture (Low Shear Modeled Microgravity/LSMMG) on microbial pathogenesis-related stress responses, in vitro host-pathogen interactions, gene expression, and virulence potential in animals using five important model bacterial pathogens, Salmonella enterica Enteritidis, Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, and enterohemorrhagic Escherichia coli. The information to date is providing a better understanding into the potential impact of microgravity on alterations in microbial virulence and associated infectious disease risk to crew health during spaceflight missions.

C M Ott↗

Spaceflight-Induced Changes in Microbial Virulence and the Impact to the Host Immune Response

Many microbial pathogen shave repeatedly exhibited unexpected responses relevant to infectious disease when grown in microgravity and microgravity analogue environments, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, host-pathogen interactions, and virulence. Notably, the classic foodborne pathogen Salmonella enterica serovar Typhimurium displayed increased virulence in animals when cultured in either the spaceflight analogue or true spaceflight environment. Recently, Serratia marcescens also was shown to increase virulence when cultured in the spaceflight environment. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system at multiple levels, which suggests an increased risk of infectious diseases. Moreover, astronauts have some degree of clinical infectious disease incidence. However, the contribution of the microgravity environment on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized. The goal of this study is to gain insight into the breadth of other medically significant microbial pathogens that may exhibit altered virulence and pathogenesis-related responses when cultured in space flight analogue conditions. Specifically, we are characterizing the effect of spaceflight analogue culture (Low Shear Modeled Microgravity/LSMMG) on microbial pathogenesis-related stress responses, in vitro host-pathogen interactions, gene expression, and virulence potential in animals using five important model bacterial pathogens, Salmonella enterica Enteritidis, Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, and enterohemorrhagic Escherichia coli. Herein, we present data from one of these pathogens, the foodborne bacterium, S. enterica Enteritidis, which is closely related to S. enterica Typhimurium. Phenotypes evaluated included growth profiles, environmental stress responses(acid, oxidative, bile, and thermal stresses),and in vitro colonization of3-D biomimetic cultures of human intestinal tissue containing immune cells. Transcriptomic profiling and virulence studies are ongoing. We show that S. Enteritidis exhibited key alterations in pathogenic responses to LSMMG culture that suggest increased infection risk, including several responses which were different from those observed in the closely related pathovar S. Typhimurium. This information will provide critical mechanistic insight into the potential impact of microgravity on alterations in microbial virulence and associated infectious disease risk to crew health during spaceflight missions.

C M Ott↗

Spaceflight-Induced Changes in Microbial Virulence and the Impact to the Host Immune Response

Many microbial pathogen shave repeatedly exhibited unexpected responses relevant to infectious disease when grown in microgravity and microgravity analogue environments, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, host-pathogen interactions, and virulence. Notably, the classic foodborne pathogen Salmonella enterica serovar Typhimurium displayed increased virulence in animals when cultured in either the spaceflight analogue or true spaceflight environment. Recently, Serratia marcescens also was shown to increase virulence when cultured in the spaceflight environment. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system at multiple levels, which suggests an increased risk of infectious diseases. Moreover, astronauts have some degree of clinical infectious disease incidence. However, the contribution of the microgravity environment on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized. The goal of this study is to gain insight into the breadth of other medically significant microbial pathogens that may exhibit altered virulence and pathogenesis-related responses when cultured in space flight analogue conditions. Specifically, we are characterizing the effect of spaceflight analogue culture (Low Shear Modeled Microgravity/LSMMG) on microbial pathogenesis-related stress responses, in vitro host-pathogen interactions, gene expression, and virulence potential in animals using five important model bacterial pathogens, Salmonella enterica Enteritidis, Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, and enterohemorrhagic Escherichia coli. Herein, we present data from one of these pathogens, the foodborne bacterium, S. enterica Enteritidis, which is closely related to S. enterica Typhimurium. Phenotypes evaluated included growth profiles, environmental stress responses(acid, oxidative, bile, and thermal stresses),and in vitro colonization of3-D biomimetic cultures of human intestinal tissue containing immune cells. Transcriptomic profiling and virulence studies are ongoing. We show that S. Enteritidis exhibited key alterations in pathogenic responses to LSMMG culture that suggest increased infection risk, including several responses which were different from those observed in the closely related pathovar S. Typhimurium. This information will provide critical mechanistic insight into the potential impact of microgravity on alterations in microbial virulence and associated infectious disease risk to crew health during spaceflight missions.

C.M. Ott↗

Analysis of Pdeudomonas aeruginosa Growth and Virulence in Modelled Microgravity

Stress, radiation and microgravity cause astronauts to experience secondary immunosuppression. Spaceflight conditions enhance bacterial growth and alter antimicrobial susceptibility. Clinostats are used to model microgravity effects at lxg. In controls rotated on the vertical axis, the g-vector acts on cells as in static cultures. Salmonella enterica serovar Typhimurium virulence genes are up-regulated in modelled microgravity (MMG); a MMG regulon has been postulated. We hypothesize that the virulence of P. aeruginosa (PA) may be affected similarly by microgravity, which could be observed in MMG. This study focused on regulation of the ETA protein by PA during growth in MMG. PA103 was grown in an ETA production medium at 37 C. One series of media was inoculated with frozen cultures and grown using horizontal (MMG) or static incubation. Another series inoculated with refrigerated cultures included vertical rotating controls. Analyses included optical density (OD), agar plate counts (PC) on R2A, ETA ELISA, and protein expression by 2-D gel analyses. Growth and ETA results differed depending on inoculum, with minor effects of MMG. Proteomic analysis of 2-D gels indicate differences in protein expression with MMG. Growth and ETA results show that consistent methodology is critical when studying environmental effects. This study provides information on the relationships between environmental changes and virulence regulation, especially for flight experiments, when ground experiments are used to predict potential spaceflight effects.

Guadarrama, Seratna↗

Influence of antiorthostatic suspension on resistance to murine Listeria monocytogenes infection

The present study was designed to evaluate the influence of antiorthostatic suspension, a ground-based modeling system employed to simulate certain aspects of weightlessness that occur during space flight, on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were suspended by the tail in the orthostatic or antiorthostatic position and were infected with a sublethal dose of virulent L. monocytogenes at various times during the suspension. It was found that suspension did not influence the kinetics of bacterial growth in vivo if the infection was started concurrently with the suspension. However, mice that were antiorthostatically suspended 2, 4, or 7 days before the onset of infection exhibited an enhanced capacity to eliminate the challenge infection. Suspending mice on day 2 of the infection did not alter the kinetics of bacterial growth. Finally, the enhancement of resistance to the primary Listeria infection was accompanied by failure of the mice to generate long-term protective immunological memory to the challenge organism. Collectively, these results indicate that the stress of antiorthostatic suspension can influence the capacity of mice to resist bacterial infection.

NASA Discipline Regulatory Physiology↗