Spaceflight is known to have profound effects on human physiology, weakening astronauts’ bones and muscles and impairing their immune systems. A new study shows that its effects on microorganisms may be just as dramatic: Salmonella grown onboard the space shuttle was many times deadlier than its terrestrial counterparts. The study suggests that NASA and other space agencies may need to worry that long manned missions will increase the virulence of microorganisms that astronauts inevitably carry with them. It has also given microbiologists insights into Salmonella that may lead to new therapies for infections on Earth.

Researchers led by Cheryl Nickerson, associate professor at the Arizona State University Biodesign Institute, found that Salmonella grown during space-shuttle mission STS-115 in 2006 underwent major changes in the expression of 167 genes. When administered to mice back on Earth, the bacteria proved many times more deadly than an equivalent strain grown on the ground.

The experiment was the first to study changes in the gene expression of a microorganism in space. The Arizona scientists provided evidence that one particular Salmonella gene regulates most of the molecular changes that the bacteria underwent. This global regulator, which seems to help the bacteria respond to stress by becoming more virulent, is a potential therapeutic target for future Salmonella treatments.

The implications for human spaceflight are not as clear. “It doesn’t seem like something NASA should worry about,” at least not in the short term, says David Robertson, director of the Center for Space Physiology and Medicine at Vanderbilt University. But it’s impossible to completely sterilize spacecraft, largely because humans carry so many bacteria around with them: bacterial cells in our bodies greatly outnumber our own. “The longer the journeys, the more we have to be concerned,” says Robertson. A manned mission to Mars, which has been proposed by President Bush, would take about three years.

The Salmonella were carried aboard the space shuttle Atlantis in a kind of suspended animation, sealed inside compartmentalized test tubes. One of the astronauts activated the bacteria cultures by pushing a plunger into a chamber that mixed the Salmonella with a growth medium. After 24 hours, the plunger was pushed into another chamber. Half the bacteria were then mixed with more growth medium to keep them alive until they returned to Earth; the other half were mixed with a chemical fixative that stopped their growth and preserved them so that their gene expression could be studied after the shuttle landed.

Researchers on the ground performed the same experiment on the same strain of Salmonella, grown in an environment that mimicked the temperature, humidity, and other conditions aboard the space shuttle but had Earth gravity. Compared with these bacteria, those grown in space displayed major changes in the activity of 167 genes and in the production of 73 proteins. Lower concentrations of the space bacteria caused lethal infections in mice, and the space bacteria killed more mice sooner than those grown on Earth.

Nickerson says that these changes may be due to mechanical stresses that microgravity imposes on the bacterial cells. In microgravity, cells in a test tube or in our bodies are in a “state of buoyancy, floating suspended,” she says. This changes the flow of fluids over the surfaces of the cells, and hence the cells’ behavior.

It seems counterintuitive that researchers can learn about how bacteria behave in our bodies on Earth by putting them in an environment as artificial as a test tube on a spaceship, says Jeanne Becker, associate director of the National Space Biomedical Research Institute, in Houston. “Looking at it from the perspective of the bacteria,” she says, “they want to be able to survive in a stressful environment”–whether it’s microgravity, an assault by the immune system, or the presence of an antibiotic. The way bacteria respond to a stressful environment–by making more or less of a particular protein, for example–can point researchers toward biochemical pathways that novel therapeutics might target.

Spaceflight also alters the genetic activity of human cells. “We evolved in a one-gravity environment,” says Becker. “There are fundamental changes when you take gravity away.” One study showed that spaceflight caused changes in the expression of more than 1,600 genes in human kidney cells grown in culture. Becker says that many more studies of the molecular effects of space conditions on cells are forthcoming, as researchers take advantage of the International Space Station.

Nickerson’s group is soon to publish papers on the effects of spaceflight on a strain of yeast and on Pseudomonas aeruginosa, the bacterium that caused the only severe infection of an astronaut to date, in 1970. To make a successful reentry into the atmosphere after an onboard explosion, the Apollo 13 astronauts retreated from the main part of their craft into their lunar module, where they faced a short supply of oxygen, power, and water. Under these extreme conditions, astronaut Fred Haise developed an aggressive prostate infection caused by Pseudomonas and was seriously ill for a few weeks after returning home.

Most infections of astronauts in space have been mild–Haise’s case is the exception–and none was caused by Salmonella. Nickerson says that she chose to study Salmonella because earlier experiments that simulated microgravity and other space conditions suggested that the bacterium’s virulence might increase in space. “While Salmonella has never been isolated from spacecraft, it’s an important reason food destined for the International Space Station gets disqualified,” she says.

“The fact that at least one nasty bug becomes demonstrably more virulent in spaceflight introduces a hazard that might before have been underappreciated,” says Kim Prisk, a professor of medicine at the NASA Lab at the University of California, San Diego. “It does make one wonder about how aggressive the medical treatment of an infected subject in space would need to be.”

More important, say Prisk and Becker, is the Arizona researchers’ identification of the global regulator of virulence that might lead to treatments for Salmonella infections. “It’s a good example of how spaceflight-oriented research can lead to potentially important and beneficial results here on the ground,” says Prisk.