Space flight has been shown to have a profound impact on human physiology as the body adapts to zero gravity environments.
Now, a new study led by researchers from the Biodesign Institute at Arizona State University has shown that the tiniest passengers flown in space—microbes—can be equally affected by space flight, making them more infectious pathogens.
“Space flight alters cellular and physiological responses in astronauts including the immune response,” said Nickerson, who led a project aboard NASA's space shuttle mission STS-115 (September 2006) involving a large, international collaboration between NASA, ASU and 12 other research institutions. “However, relatively little was known about microbial changes to infectious disease risk in response to space flight.”
Cheryl Nickerson and lead author James Wilson, both professors in ASU's School of Life Sciences, have performed the first study of its kind to investigate the effect of space flight on the genetic responses and disease-causing potential, or virulence, of Salmonella typhimurium, the main bacterial culprit of food poisoning. Their results, published in the journal Proceedings of the National Academy of Sciences (www.pnas.org.cgi/doi/10.1073/pnas.0707), reveal a key role for a master regulator, called Hfq, in triggering the genetic changes that show an increase in the virulence of Salmonella as a result of spaceflight. The results of these studies hold potential to greatly advance infectious disease research in space and here on Earth, and may lead to the development of new therapeutics to treat and prevent infectious disease.
To study the effects of space flight, Nickerson and colleagues sent specially contained tubes of Salmonella in an experimental payload aboard the Space Shuttle Atlantis. The tubes of bacteria were placed in triple containment for safety and posed no threat to the health and safety of the crew during or after the mission.
During the flight, astronaut Heidemarie M. Stefanyshyn-Piper activated growth of the bacteria in sealed hardware and ‘fixed' the cultures after a day of growth to determine changes in gene and protein expression levels.
“The bacterial cultures were taken up into space and activated to grow in a separate compartment of the tubes called the growth chamber,” said Nickerson. “The bacteria didn't have access to the growth chamber until Heide pushed down on a plunger which introduced the bacteria into the growth media. Then they were grown for 24 hours, and at the end of 24 hours, Heide pushed down on the plunger again, which either “fixed” the bacteria with chemicals that preserved the gene expression message, or else introduced fresh media to keep the bacteria growing to perform the virulence studies.”
As a synchronous control experiment back on Earth, Nickerson's team grew an identical set of bacteria in the same type of tubes used for flight and incubated them in a special room at the NASA Kennedy Space Center called the orbital environmental simulator. “This simulator is linked in real-time to the shuttle, and duplicates the exact temperature, humidity and growth conditions of the shuttle, with the exception that they are not flying in space,” said Nickerson. “In addition, we were also linked via real-time telecommunications with the shuttle crew when they were activating and terminating our experiments in flight, and we did the exact same things at the same time to the ground samples that the astronauts did to the flight samples – thus we had perfectly matched synchronous ground controls.”
After the bacteria returned to Earth, the group performed the first global analysis of Salmonella to measure the effect of space flight on gene and protein expression and virulence. By measuring the gene and protein patterns, the researchers could hone in on the key molecular players necessary for virulence from among thousands of potential candidates.
“We chose to measure gene expression at the mRNA level since the technique to do this, called microarray analysis, is a highly advanced and convenient way to quantitatively measure the expression of every gene in a single experiment,” said Wilson, who coordinated the team's molecular profiling efforts for the Nickerson lab, and played a central role in the performance of these experiments, including data analysis. “It is a very powerful technique that was very applicable to the spaceflight experiment. The isolation of mRNA poses particular challenges since it is very sensitive to degradation, but we designed the experiment using a fixative that preserved the mRNA very well.”