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Alterations in the virulence potential of enteric pathogens and bacterial-host cell interactions under simulated
1Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-1070, USA.
Abstract:
Host immune mechanisms were proposed to decline under microgravity conditions during spaceflights, which might result in severe infections in astronauts. Therefore, it was important to investigate the effects of microgravity on infecting organisms and their interaction with host cells. Data showed that simulated microgravity (SMG) conditions markedly increased production of the enterotoxigenic Escherichia coli (ETEC) heat-labile enterotoxin, which induced fluid secretory responses in a mouse model. SMG also enhanced production of tumor necrosis factor-alpha in murine macrophages infected with enteropathogenic E. coli (EPEC). In a similar fashion, simulated microgravity conditions augmented the invasive potential of Salmonella enterica serovar typhimurium and enhanced production of tumor necrosis-factor alpha in S. typhimurium-infected epithelial cells. Furthermore, coculturing of macrophages and S. typhimurium in a simulated microgravity environment resulted in activation of stress-associated mitogen-activated protein kinase kinase 4. Using the antiorthostatic tail suspension mouse model, which simulates some aspects of microgravity, oral inoculation of S. typhimurium markedly reduced the 50% lethal dose compared to mice infected under normal gravitational conditions. Microarray analysis revealed simulated microgravity-induced alterations in the expression of 22 genes in S. typhimurium, and protein expression profiles were altered in both EPEC and S. typhimurium, based on two-dimensional gel electrophoresis. These studies indicated alterations in the virulence potential of bacteria and in host responses to these pathogens under simulated microgravity conditions, which may represent an important environmental signal. Such studies are essential for better understanding bacterial-host cell interactions, particularly in the context of spaceflights and space habitations of long duration.
Insights
Microgravity enhances bacterial virulence and host immune responses, increasing infection risks for astronauts. This research highlights how spaceflight conditions can alter pathogen behavior and host interactions, crucial for long-duration missions.
Area of Science:
- Microbiology and Immunology
- Space Biology
- Infectious Diseases
Background:
- Host immune mechanisms may be compromised in microgravity, increasing astronaut susceptibility to infections.
- Understanding the impact of microgravity on host-pathogen interactions is critical for space exploration.
- Previous research suggested potential immune system alterations during spaceflight.
Purpose of the Study:
- To investigate the effects of simulated microgravity (SMG) on bacterial virulence and host-pathogen interactions.
- To assess changes in bacterial toxin production and host immune responses under SMG conditions.
- To evaluate the impact of microgravity on the infectivity and lethality of common bacterial pathogens.
Main Methods:
- Utilized simulated microgravity (SMG) models, including antiorthostatic tail suspension.
- Infected murine macrophages and epithelial cells with enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli (EPEC), and Salmonella enterica serovar typhimurium.
- Analyzed bacterial toxin production, host cytokine responses (e.g., TNF-α), gene expression (microarray), protein profiles (2D gel electrophoresis), and pathogen lethality (LD50).
Main Results:
- SMG significantly increased ETEC enterotoxin production and induced fluid secretion.
- SMG enhanced EPEC-induced tumor necrosis factor-alpha (TNF-α) production in macrophages.
- SMG augmented S. typhimurium invasion, epithelial cell TNF-α production, and macrophage stress kinase activation.
- S. typhimurium infection showed a reduced LD50 in SMG-simulated mice.
- Microarray and proteomic analyses revealed significant alterations in bacterial gene and protein expression under SMG.
Conclusions:
- Simulated microgravity conditions alter bacterial virulence factors and enhance host responses to infection.
- These findings suggest microgravity acts as an environmental signal influencing bacterial-host cell interactions.
- Understanding these changes is vital for mitigating infection risks in astronauts during long-duration spaceflights and future space habitats.
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