Bacteria More Virulent in Microgravity

Tortured Potato writes "Did you know that salmonella become more virulent in simulated microgravity? No one's sure why, either. Professor Cheryl Nickerson of Tulane University is hoping to find out why when an experiment with brewer's yeast gets sent up on a Russian Progress rocket to the Space Station next year."

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Life is a bit different in space, even for microbes. Research shows that the pattern of gene activity in some microbes differs in weightlessness, leading to differences in behavior. These differences could be behind a curious observation: the common food-borne pathogen salmonella becomes more virulent when grown in a form of simulated microgravity.

This news is little comfort to astronauts whose immune systems already function below par in weightlessness, making infection more likely. To help keep astronauts healthy and to better understand microbial infection in general, scientists want to know exactly which genes are affected by microgravity and why weightlessness--whether real or simulated--should cause these changes.

"Whenever you see the virulence of a microbe change in response to an environmental stimulus, that's a chance to learn something about how that pathogen causes disease," says Cheryl Nickerson, an expert in microbiology and immunology at Tulane University Health Sciences Center.

Nickerson and her colleagues hope that studying these changes could point out new ways to combat "bad" microbes with drugs and vaccines, both for the sake of astronauts and for people here on the ground. Using modern advances in biotechnology and the weightlessness provided by the International Space Station (ISS), they plan to explore the changes in gene expression experienced by microbes in the true weightlessness of spaceflight.

Their first experiment, called "Yeast GAP", will send genetically engineered brewer's yeast (Saccharomyces cerevisiae) up to the space station aboard a Russian Progress rocket in 2004.

Brewer's yeast itself is not pathogenic. Nevertheless, "yeast cells make a great 'model organism' for this research because they're easily handled, thoroughly studied, and their genome has been completely mapped," says Nickerson, the principal investigator of Yeast GAP. Furthermore, brewer's yeast shares much of its DNA with infectious species of microscopic fungi and protozoans. "Also, the yeast's genome is relatively simple, which makes the results easier to analyze," she says.

Still, the challenge is formidable. The brewer's yeast genome contains 6,312 genes, each of which produces one of the proteins that constitute the molecular machinery of the cell. To get a grip on this immense complexity, the researchers will send up 6,312 variants of the single-celled yeast. Each variant has a different gene "knocked out" and replaced with a unique "barcode" pattern of custom-made DNA. This barcode DNA does not encode a protein; it merely serves as a tag distinguishing that particular variant from all the others.

"We mix all these different strains of yeast in a special growth apparatus (called the Group Activation Pack, hence the acronym GAP) and see which ones grow well in weightlessness," explains Timothy Hammond, co-investigator for Yeast GAP and a kidney specialist (nephrologist) at Tulane University Health Sciences Center and the Veterans Affairs Medical Center in New Orleans.

Suppose a yeast variant is missing some particular gene--let's call it "gene X." And suppose that variant fails to grow as well in space as it does on the ground. Such a result would imply that the missing gene X is an essential part of the yeast's response to microgravity.

That little nugget of knowledge would then help guide future research: scientists could target their experiments to see how the protein produced by gene X relates to the changes in various microbes' behaviors in space--including microbes that cause disease. It would also help to explain the explosion of STD's in the Ann Arbor MI area.

Why should any kind of cell behave differently in microgravity? No one's sure, but scientists have some ideas. For example: perhaps cells sense deformations in their sack-like membranes and respond to that signal. Cells cultured in 1-g normally settle to the bottom of their container and become flattened, while cells floating in weightlessness remain more round. That diff