Like a Kubrickian psychodrama retold at the microbial scale, zero-gravity physics seems to trigger salmonella's dark side, making the food-poisoning bug more virulent when cultured in space.

But there may be a happy ending: Depending on what salmonella itself is fed, it can become less virulent — a trait that hints at new ways of weakening Earthly disease.

"There's more to this than worrying about food poisoning in space," said Arizona State University microbiologist Cheryl Nickerson. "We're opening new doors to understanding how pathogens in general are causing disease."

Nickerson showed last year that salmonella became more contagious when cultured during a space shuttle voyage. Upon returning from a ride on the STS-115 space shuttle, unusually low doses were needed to infect mice: zero-gravity fluid dynamics seemed to trigger the same microbial attack mechanisms typically stimulated by the movement of fluid in our guts.

The salmonella used in that research were grown in a nutrient-rich medium. Well-fed salmonella shot into space for Nickerson's latest study, published recently in PLoS One also became extra-virulent. This time, however, she also included a low-nutrient salmonella culture — and those bacteria proved to be far less virulent than their well-fed counterparts.

In both cultures, many of the same gene families were triggered, suggesting some sort of common master regulator that determines the response of salmonella to its environment. If that function exists in other bacteria and can be manipulated by scientists, it could be tweaked to make them less able to cause disease.

"By identifying specific molecular mechanisms by which these organisms respond to stimuli in the space environment," said Michael Roberts, a NASA microbiologist who was not involved in the study, "the group has identified potential therapeutic targets for limiting the bacteria’s virulence inside our bodies."

Also included in the latest experiment, carried on the March 2008 space shuttle mission STS-123, was a hybrid solution rich in five nutrients suspected by Nickerson of altering virulence: phosphate, magnesium, sulfate, chloride and potassium.

Salmonella grown in this broth proved weak, and further testing in lab-simulated zero-gravity environments suggests that phosphate may be especially important for reducing virulence. That finding dovetails with another observation of Nickerson's: the master Hfq protein that controls dozens of other genes activated during the experiment is linked to phosphate uptake and may be a common response regulator to this environment.

"We don't have a complete mechanistic understanding of this process, but we have some exciting clues," she said. "There are lots of bits and pieces that allow us to start putting together the puzzle."

Roberts called the research "interesting and highly important." He noted that it could also be useful for protecting astronauts and future space explorers.

"As we leave Earth to explore space and establish a sustained human presence beyond low-earth orbit, our constant companions will not only be along for the ride but will be evolving during the journey," Roberts said.

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Media Ion Composition Controls Regulatory and Virulence Response of Salmonella in Spaceflight [PLoS ONE]*

Image: Salmonella bacteria (grown on Earth, not in space) / University of Wisconsin

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