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Space: A Bad Influence on Microbes?

At least one common disease-causing microbe becomes more virulent in simulated microgravity. Scientists studying this phenomenon hope to gain a better understanding of infectious disease.

by Patrick L. Barry

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.

Image courtesy Avinash Abhyankar

A false-color micrograph of the disease-causing microbe salmonella

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.

Image courtesy David Byres, Florida Community College at Jacksonville

The single-celled fungus Saccharomyces cerevisiae, also known as brewer's yeast.

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.

Image courtesy NASA

Growing cells remain suspended in microgravity - a difference from ground-based cultures that could be cueing differences in gene expression.

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 difference could be cueing changes in gene expression.

Nickerson and others are exploring this idea on the ground using a "microgravity simulator" developed by NASA's Johnson Space Center. Called the "rotating wall vessel bioreactor", it mimics the conditions of weightlessness for microbes by growing them inside of a slowly rotating liquid-filled chamber. The rotation of the liquid counteracts the slow sedimentation of the cells, thereby creating a constant "free-fall" of the cells through the culture medium. Cells feel a slight shear as they move through the liquid - a difference from true weightlessness that could affect their behavior - but like cells in orbit, they avoid becoming flattened on the bottom of the container. (It was using this bioreactor that Nickerson first noticed the increased virulence of salmonella.)

Apparently, the bioreactor's approximation of weightlessness works rather well. An earlier experiment by Hammond showed that a strain of brewer's yeast grown on the ground in the bioreactor showed many of the same changes in behavior as yeast grown onboard the space shuttle. Exploring the similarities and differences in how cells react to this bioreactor environment versus true microgravity will be another important outcome of Yeast GAP, Hammond says. If the rotating bioreactor proves sufficiently similar to the orbital environment, it could provide a cheaper and more convenient way to study microbes in microgravity-like conditions.

Whether performed in true or simulated weightlessness, this line of research could help unravel the genetic basis of infection - a bit of knowledge that would help astronauts and land-lovers alike to live a little healthier.


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First Science 2014