NIH

Mineral studies advance antibacterial alternatives

kakeane — Fri, 12 Mar 2010 13:30:47 -0700

ASU School of Life Sciences undergraduate Jenny Koehl and microbiologist Shelley Haydel investigate the chemistry and killing power of clays with antibacterial activity.

by Margaret Coulombe

Alternative approaches to medicine are stock-in-trade in the ASU laboratory of microbiologist Shelley Haydel.

So when ASU senior Jenny Koehl joined Haydel’s investigative team seeking firsthand knowledge of how basic research is done, how drugs are tested and potential cures produced, she found it and much more.

With the guidance of Tanya Cunningham, a graduate student mentor, Koehl has helped advance understanding about the antibacterial activity of clay minerals and their ability to kill what the best antibiotics on the market can’t touch.

Haydel’s group collaborated with Jack Summers, an inorganic chemist at Western Carolina University. They uncovered two factors that control the antibacterial activity. Their work was published in the March 1 issue of Public Library of Science (PLoS) ONE.

“This work sets a baseline from which to look for potential mechanisms of antibacterial action,” said Cunningham, lead author, who is now a research technician with the Fred Hutchinson Cancer Research Center in Seattle.

“We need helpful alternatives, natural approaches to antibacterial cures, because there is bacterial resistance to drugs,” Koehl said. “Knowing the mechanisms of action will help us develop our own topical treatments.” Clay has had a role in human health as ancient as man. However, specific identification of the mechanisms underlying this antibacterial activity has been elusive, until now.

The Haydel-Summers collaborative has added clarity to these distinctly muddy waters by screening more than 50 mineral mixtures (and aqueous extractions from them, known as leachates) marketed as health and cosmetic products using pathogens Escherichia coli, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa. Only two mineral mixtures of significantly different compositions (and their leachates) were discovered to possess antibacterial traits.

Clay minerals often are recognized as the slimy slurry that slicks riverbanks. Understanding clay’s structure is integral to answering questions about the mechanisms behind its antibacterial activity. Negatively charged surfaces attract positively charged elements, such as iron, copper, silver and other metals. In turn, water is absorbed between layers of the crystal structure creating a cation sandwich with aqueous filling or interlayer. Antibacterial activity in leachates, extracted from the mineral mixtures, confirm that the antibacterial activity is chemically-based, rather than a result of physical interactions with microbes.

Because of the tendency of clay to attract multivalent ions, particularly metals, the scientists next examined the leachates’ chemistry and antibacterial activity in the presence of chelators, which bind metals. The researchers also used thiourea, a hydroxyl radical scavenger, at various pH levels. Chelation of the minerals with ethylenediaminetetraacetic acid (EDTA) or desferrioxamine eliminated or reduced toxicity, respectively.

Further testing of the mineral leachates confirmed that there are higher concentrations of chemically-accessible metal ions in leachates from antibacterial samples than from non-bactericidal mineral samples.

In addition, acidic conditions were found to increase the availability of metal ions and their toxicity. Overall, these findings suggest a role of an acid soluble metal species, particularly iron or other sequestered metal cations, in mineral toxicity. However, whatever advances the study puts forward also present researchers with further challenges. Acidity may complicate development of topical treatments, if neutral pH, least damaging to skin and tissue, also reduces the mineral’s antibacterial action.

Another complicating factor is that chemical environments under which any particular clay can emerge can greatly influence its toxicity, adsorptive qualities and, according to their findings, its antibacterial effects.

“Because natural mineral mixtures can be variable, both mineralogically and chemically, we must continue to define specific chemical properties that influence the antibacterial effectiveness,” Haydel said. “Our goal is to understand the details, so we can, in the future, perhaps generate mineral mixtures that mimic the chemical compositions and environment, so that the antibacterial activity can be controlled and ensured.”

This work is about eliminating the unknowns,” Koehl said. “We have more analysis to do, looking at the leachate composition, the action of the chelators and activity of the iron scavengers.”

Koehl, who is working with Haydel as part of the School of Life Sciences Undergraduate Research (SOLUR) program, said of her experience: “Science is like an obstacle course. I’ve learned that when you come across problems in the laboratory, you have to be creative to work them out. This process has helped me be more critical, to be a thinking scientist, because I’ve had to analyze my own experiments and figure them out. This isn’t just something that someone handed to me on paper in a classroom.”

Studies are moving forward in other laboratories to develop structured clays for slow-release topical medical treatments, but there may be chemical schemes that come from Haydel’s research that enhance their effectiveness.

“This study has given me an idea of how things move from idea to shelf,” Koehl said. “One day, when I am a pharmacist, maybe I’ll be selling this!”

This work is supported by the National Institutes of Health. Haydel’s group is part of the School of Life Sciences, in the College of Liberal Arts and Sciences, and the Biodesign Institute at ASU.

Read the article in PLoS ONE.

Stimulated to heal

ovprea — Mon, 09 Mar 2009 12:47:39 -0600

by Melissa Crytzer Fry

Shelley Savage considers herself lucky. Despite having to rely on a wheelchair for the past 15 years, she knows that things could have been worse—possibly much worse. Savage was a passenger in a car accident during her college years. She broke her neck at the C6 vertebra.

The break was classified as an incomplete spinal injury. "Incomplete" means that some nerves are still connected above and below the injury site. For Savage, that equates to upper body control and some sensation throughout her lower torso.

"I was completely paralyzed for the first three months, so I know what a complete spinal injury is like," says the optimistic 38-year-old. "I am very grateful to have gotten some movement and feeling back in my body. It's still tough sometimes. But I'm able to have more independence and freedom."

Savage has never given up hope for a cure. She'd be lying, though, if she said the road has been easy.

"It's frustrating and discouraging. Once you become paralyzed, you're basically written off. You're told Ã¢â‚¬ËœThis is it. Don't expect much.'"

In addition, Savage says that physical therapy is only offered early after the injury. She also learned that reduced activity after a spinal cord injury can also lead to other complications. At age 30, she developed osteoporosis-related bone loss, despite a desire to remain actively engaged in physical therapy.

"You really have to fight for follow-up physical therapy," she explains. "Sometimes the only way you get the therapy is if you injure yourself."

Even then, therapy is offered at only a limited number of clinics. Most of that is on bulky and unaffordable exercise equipment.

James Abbas and Ranu Jung are working to change that scenario. Abbas and Jung are bioengineering professors at Arizona State University. They are co-directors of ASU's Center for Adaptive Neural Systems. Their research is focused on the use of electrical stimulation to contract paralyzed muscles.

Abbas and Jung are designing adaptive technology that actually interacts with the nervous system. The goal is to create devices that promote recovery and reorganization of the nervous system after spinal cord injury.

In one study, the ASU researchers are testing a hand-held muscle stimulator. The device is called CK200. It was developed by customKYnetics, Inc., a commercial partner working with the ASU engineers. Abbas is co-founder and part owner of the company. His efforts are focused on testing and understanding the company's products.

The CK200 is about the size of a paperback novel. It uses electrical stimulation to activate the muscles. Adhesive electrodes connected to the CK200 are placed on the skin. When activated, current passes through the electrodes and into the muscle, causing a muscle contraction.

"The idea is really based on a simple therapeutic principle. Do something. Be active. That's the best way for muscles to re-learn how to work," Abbas explains.

Participants in the ASU study had both complete and incomplete spinal cord injuries. Each person each received a hand-held CK200 unit for home use over the course of three months. After completing initial evaluations at ASU, they returned monthly for additional readings.

During each session, participants completed 60 muscle stimulations. Ankle weights were added periodically. When a subject could successfully complete three sessions without fatiguing the muscle, the weight was increased by a half-pound.

Members of the complete spinal injury group worked to stimulate the quadriceps muscles on each leg. The goal was to gain ability to complete standard leg lifts.

"This wasn't an aggressive therapy, although participants were getting some exercise and increased muscle strength," explains Abbas. "It was meant as an initial test of the device. We wanted to determine if it could generate smooth contractions of paralyzed muscles, and if the muscles got stronger."

The goal was different for the group with incomplete spinal cord injuries. The researchers wanted to know if participants were gaining the ability to voluntarily contract the muscles being targeted by the CK200.

"People with incomplete spinal cord injuries have great potential for relearning, which can impact their daily lives," Abbas says. "The thought is that, after repetitive muscle movement with the device, they'll eventually be able to control more and more of that movement, and hopefully wean off the stimulation."

The ASU study revealed that participants' muscles definitely got stronger through CK200 usage. Savage volunteered for the trial. She saw great gains for herself.

Early in the study, she could not complete a full set of leg extensions without ankle weights. At the end of three months, with the stimulator, she could complete the full set with five-pound ankle weights on each leg.

"I could feel the muscle tightening—the same kind of burn you feel if you've been lifting weights," Savage explains. "I wasn't even sure I had any muscle left after all these years. It was encouraging to realize that maybe the muscles weren't completely gone."

During the course of the study, the muscle mass in Savage's thighs increased by 11 percent.

"The numbers for individual participants progressed as the session went on," says Abbas. By the end of 2008, seven subjects had completed the full study. Six of those people reached the five-pound ankle weight maximum on at least one leg, with a muscle mass gain of at least 4 percent.

Researchers say that the health benefits of stimulation therapy can't be overlooked.

"Stimulation helps with the blood circulation in that region. It improves the overall health of the skin and muscles," adds Jung.

Muscle stimulation can also positively impact immune system response and hormonal response. What's more, such activity may be able to stave off diabetes and heart disease for people with paralysis, who are more susceptible to those diseases.

"Devices that use electrical stimulation exist in the marketplace. But they require someone to preset the values," explains Abbas.

For example, a physical therapist has to hand-set the controls before and after each and every desired movement. The CK200 is different. It has smarts as part of its internal computer that control the stimulation. The hand-held device continually adjusts the level of stimulation to achieve the desired movement pattern.

"It's personalized to each person who uses it," explains Abbas. It can sense when a muscle is fatigued and adjust the amount of stimulation on the next repetition—to maintain the same controlled movement.

But how does this smart technology actually work? Abbas says that CK200 uses an adaptive algorithm—a formula—programmed into the device, to compare the person's patterns of movement.

"The sensors on the skin read the movement patterns generated by the muscles," explains Jung. "The computer reviews that movement and compares it against a desired pattern of movement."

Preset with specific movement patterns, the CK200 stimulator can detect any movement errors and automatically adjust the pulses sent through the electrodes.

"The algorithm basically allows us to get the movement we're asking for," Abbas adds. He developed the basic adaptive algorithm used by the CK200.

"Initially, I was focused on programming the computer. I wasn't worried about making it smaller," Abbas continues. "But then I asked myself, Ã¢â‚¬Ëœwhat if we use this technology in a simple device for exercise?'" That question led to the birth of customKYnetics, Inc.

"We know the body is trying to heal itself during a spinal injury," explains Jung. "And we know neural systems can adapt—at the gene level, protein level, and cellular level. We're also trying to understand how and why that happens. And what can we do to promote that? Do stimulation devices expedite that process?"

Results from the initial studies hint that the answer is "yes." But the ASU bioengineers know their work is in its infancy. Currently, test participants included only those with spinal injuries that occurred years ago. Future studies may reveal that the potential for recovery increases if stimulation is introduced immediately after injury.

"We had to start with stable, healthy individuals. We had to know that it was the device helping them, and not the natural recovery process seen in the first few months after injury," explains Abbas.

One thing is certain: as the studies change in design, so, too, will the evolution of portable stimulation devices like the CK200. In the future, the device may even have applications for knee injury rehabilitation, and for more aggressive therapy programs. Someday, it is hoped these devices will be accessible and available for home use.

As Shelley Savage says, "They're getting close. Any progress being made brings us one step closer to a cure." When she walks again—not if—Savage says her first steps will be among Europe's medieval castles.

ASU studies on neuromuscular are supported by the National Institutes of Health and Science Foundation Arizona. For more information, contact James Abbas, Ph.D., or Ranu Jung, Ph.D., ASU Center for Adaptive Neural Systems, Ira A. Fulton School of Engineering, 480.965.9521 or 480.965.9052. Send e-mail to: Jimmy.Abbas@asu.edu and Ranu.Jung@asu.edu

Symbionts of success

ovprea — Mon, 26 May 2008 11:00:00 -0600

by Margaret Coulombe

Stan Faeth has spent the past 27 years as a professor of life sciences at Arizona State University. He was hired as a professor straight out of graduate school. But despite interests in geology and paleontology, a career as a professor was not in his plans while growing up in Kentucky. It all began a bit differently for Faeth.

Was he a budding Jacques Cousteau wannabe? No way. Faeth was always more of an outdoorsy Jack Kerouac, the confessional-style poet of the Beat Generation who traveled aimlessly across the United States. Faeth hitched his way across the U.S. and Canada after earning his undergraduate degree. He traveled where fate or the road led him.

Fortunately, the road led to professor Thomas Kane at the University of Cincinnati in Ohio. Kane became Faeth's master's degree mentor.

Kane was a well-loved and respected evolutionary ecologist who studied cave invertebrates. He passed away in 2007. Faeth was Kane's first graduate student, and he credits the UC professor with setting him on his path to ASU.

"I wasn't particularly focused," Faeth says. "I was interested in microbial ecology, but I was young, green, and naive. He helped rein me in and introduced me to insects. I would never have survived without Thomas Kane."

Kane directed Faith's budding environmental interests toward the pursuit of understanding a tier of intertwined ecological relationships. What exactly are the interactions between microbial symbionts, plants, herbivores, and predators? The work has led Faeth in directions ranging from birds to cancer cures.

Symbionts and ecosystems
Microbial symbionts include small fungi, bacteria, and viruses. Faeth says they are found in nearly all organisms. They exist in the guts of animals, the interiors of corals, and the roots of plants.

One example is the mycorrhizae that live in the belowground parts of corn and other. The symbionts enhance nutrient uptake. Another example is the bacteria that live in the guts of termites and cows. The bacteria actually break down cellulose from the wood or plant material eaten by the insects or animals. In these cases, both the host animal and the bacteria mutually benefit.

The results are not always beneficial. Faeth says that the effects of symbionts on the host can run the gamut from mutualistic to pathogenic. He points to the imported fungus responsible for chestnut blight.

"Chestnuts were once a dominant tree in the eastern deciduous forest," Faeth explains. "The trees were an important food source for insects, animals, and Native American populations." The fungus eliminated chestnut trees from North America.

Faeth is fascinated by the range of effects that fungal symbionts can potentially have on their hosts, and how those relationships evolved. He has a particular interest in the grasses native to Arizona.

Fungal symbionts are called endophytes. They are found in many different plants. Endophytes can live on bark, leaves, stems, and roots. They are primarily found in the aboveground parts of grasses.

Some symbiotic bacteria are well understood. They fix nitrogen in legumes and mycorrhizae in the roots of many plants that increase nutrient uptake. As a result, they provide a nice a source of fertilizer. But endophytes in grasses produce some unusual chemicals. The effects of these chemicals are less clearly understood. Scientists call these chemicals "secondary metabolites."

In many systems, Faeth says these metabolites have been found to be detrimental to plant-eating animals. The relationship between the endophyte and the plant grass is a benefit to both. Distasteful leaves mean fewer animals chomping away and better plant survival, right? However, as with all relationships, Faeth is proving that things are much more complicated than previously believed. The effects are far-reaching.

"Endophyte infections in grasses can cause shifts in the diversity, abundance, and species compositions of entire communities," Faeth says. They can affect the plant eaters, the predators, the parasites, and the scavengers.

Sleepy grass, LSD, and cancer cures
Ergot alkaloids provide a great example. The alkaloids are chemicals produced by fungus on plants. These chemicals are better known as lysergic acid diethylamide, or LSD for short.

The hippy-era fascination with LSD spawned a bevy of human social byproducts: acid rock, Haight Ashbury, and the Summer of Love in 1967.

Ergonovine is another potent alkaloid produced by the fungal endophyte Neotyphodium. Both have played a role the evolution of grasses, their herbivores, and their predator communities.

Faeth was one of the first researchers to ask these questions about native grasses. His group studies two grasses native to Arizona. Arizona fescue (Festuca arizonica) is one. The other is robust needle grass (Achnatherum robustum), also known as sleepy grass. The plant gets its name for its sometimes narcotizing effect on grazing cattle and horses. It is not hallucinogenic. In fact, in early South American cultures, mothers would calm their infants by giving them a single grass seed to eat.

So would Old Paint benefit from a trip to this field of greens? Faeth says that vertebrates avoid sleepy grass. But what about insects and other arthropods?

Faeth's experimental fescue plot has red cones placed to permit aeration of the soil in treatments designed to restrict water availability. Some plants are also caged to exclude herbivores.

Faeth has a study site at the Arboretum in Flagstaff. A trip there helps tell the tale. At first glance, the abundance of red inverted funnels and wire cages weighted with rocks looks artfully indecipherable. However, four different genotypes of plants are laid out in a carefully planned grid. In each year-long study, a total of 240 experimental and 30 control plants are examined. Tufts, with and without fungal endophytes, are tested to determine the effects of rainfall, irrigation, drought, and herbivores (or lack of herbivores). Faeth's findings have been surprising.

"These endophytes are usually considered evolutionary dead ends," Faeth explains. "They are asexual and they attract arthropod herbivores, rather than repel them. This effect can vary with environmental factors like fire, drought, nutrients, etc. This might regulate the endophyte-plant-herbivore-predator community structures from site to site."

Such findings go against those found in other systems and studies. But Faeth has a theory about that, too.

Lots of people prune their trees and cut their grass. The ASU scientist says that cutting creates more reproductive structures and grass seeds.

"In native grasses, we believe that endophytes may be encouraging herbivory, or the eating of the plants. This helps to produce more seeds and more opportunity for endophyte-infected seeds to be distributed—even at the long-term expense of the plant," Faeth says.

The enemy of my friend is my friend? It's an evolutionary twist that yields more seeds, more grass, more endophytes, more herbivores, more predators, and more overall abundance in a community—all manipulated by a microscopic organism.

Faeth's work on these tiny microbes, their chemicals and desert plant hosts has led to other discoveries: anti-cancer agents. Leslie Gunatilaka is a natural products chemist at the University of Arizona. She and Faeth have screened a range of native plants and shrubs for endophytes. They've also analyzed their associated metabolites.

The scientists found potent anti-cancer agents in two plants. Extracts from the stick-like Mormon Tea and the cholla Christmas cactus yielded beauvericin, bikaverin, and other anti-cancer compounds.

Faeth is quick to point out that this is not an entirely unknown phenomenon. The yew tree contains the anti-cancer agent taxol. Scientists now think that the chemical comes from endophytes in the bark of the yew, rather than from the plant itself.

The findings by Gunatilaka and Faeth mean that Arizona native plants and their microbial partners may represent an untapped treasure trove of compounds. These chemicals may have the potential to impact human health and control disease. But first, the plants must be conserved.

Urban ecology and conservation
Urban areas in the Southwest are expanding rapidly. Growth in the Phoenix metropolitan area is faster than most regions in the world. Urban sprawl puts tremendous pressure on surrounding desert landscapes and animals. Still, little is understood about urbanization's potential long-term effects on the environment and how best to assess its conservation. Faeth's work is about understanding basic patterns of biodiversity and food webs in urban habitats.

The ASU scientist's research and that of his colleagues are busting myths. The findings offer novel ways to assess and understand our urban environments and their impact on Arizona's wild areas.

Faeth says that things are often not what they seem in urban areas. For example, some landscapes look like deserts or desert remnants. These are areas that we preserve. Other yards are built to look like deserts. But these areas don't really function like desert land anymore.

"Human activities have caused this uncoupling. We are changing nutrient availability," he explains. "There are nitrogen pollutants from agriculture and in aerosols from cars and even fast food. And urban xeriscapes tend to have higher productivity because people water their yards nearly as often as they might grass. Consequently, there are more herbivores, more types of insects, and a greater abundance of birds that prey on them.

"Things are also shifted seasonally in the cities," he continues. "Instead of going through the boom and bust that you normally find in the desert, things are in bloom all year round."

The array of interactions and impacts can be very confusing. So what is the best way to approach issues of biodiversity, conservation, and preservation in our deserts and urban areas?

Faeth hopes that insights from his group's studies will provide solutions. They've already contributed plenty over the years. Getting more useful answers may only be a matter of Faeth.

Stan Faeth's research is supported by the National Institutes of Health, National Science Foundation, and the Arizona Disease Control Research Commission. To hear Faeth speak more about his work, go to the Ask-a-Biologist Web site: http://askabiologist.asu.edu/podcasts/index.html#Faeth

Space ills and Earth cures

ovprea — Thu, 15 May 2008 15:10:15 -0600

by Margaret Coulombe

Color-enhanced scanning electron micrograph showing Salmonella typhimurium (red) invading cultured human cells: Photo courtesy of Rocky Mountain Laboratories, NIAID, NIH

The technology created by NASA scientists and engineers has done plenty to help humanity over the past five decades. All that brainpower and technical know-how has spawned and improved satellites. It has also led to the creation of flat-screen televisions, robotic wheelchairs, water purification systems, and cell phones. Could it now also hold the key to what ails us here on Earth?

Cheryl Nickerson has bet her career on it. Nickerson is an earthbound microbiologist at Arizona State University. She also is an associate professor in the School of Life Sciences and researcher in the Biodesign Institute at ASU. Her NASA-funded research supports the development of innovative experimental models for infectious disease and drug development, on Earth and in space.

Nickerson wants to transform our understanding of the forces that shape nasty little pathogens and their ability to cause disease.

"Those tax dollars we invest in NASA's manned space programs propel new product discovery that impacts our lives on a daily basis, including advances in health and medicine," Nickerson says. "So the fact that we have the potential to provide novel cures and therapeutics to treat infectious diseases as a result of the manned space program should come as no surprise."

It was a natural leap for Nickerson to look to space and beyond the bounds of Earth to ask new questions about disease. The ASU scientist qualified as an astronaut candidate finalist in 2004.

Past studies have shown that microbial contamination presents a real health threat in space, just as on Earth. The presence of disease-causing microorganisms aboard spacecraft is well documented. Infectious disease events have occurred in flight. For example, a crewmember on the ill-fated Apollo 13 mission to the moon suffered a debilitating urinary tract infection.

The close quarters aboard both the Space Shuttle and International Space Station (ISS) can be a factor leading to sickness and infection. So is the recirculated water and air. Crew members from different countries can also lead to problems. The people carry microbes native to their geographical locations. All are factors that increase the potential for exposure to infectious pathogens.

Scientists know that spaceflight also weakens the immune system, Nickerson says. There are reports of increased microbial resistance to antibiotics during spaceflight. In fact, according to NASA, approximately 25 percent of all Space Shuttle missions have had at least one crew member affected by a minor infectious illness.

Other big questions remain unanswered about how the pathogens themselves are affected by space travel:

Does outer space affect their disease-causing potential?

Do pathogens behave in the same way in space as on Earth?

Nickerson is one of the first to look for answers to these questions. She uses ground-based analogues of spaceflight. The main tool for this work is called a rotating wall vessel bioreactor (RWV). She also is translating the work into true spaceflight experiments on board the Shuttle and ISS.

How did Nickerson's "out-of-this-world" thoughts about science and pathogens first take flight? She says that she always knew she would become a scientist. She credits her parents for encouraging her intellectual curiosity.

"I always wondered how things worked. I took them apart—though I didn't always put them back together correctly," Nickerson explains. "And I grew up reading the books in my father's extensive science library—I was hooked."

Nickerson's father, Max, is one of the world's leading authorities in vertebrate zoology and herpetology. He is curator of the Florida Museum of Natural History at the University of Florida in Gainesville, and an ASU graduate.

Years of family nature walks also helped. The Nickersons hiked deserts, forests, and mountains. Conversations about what flora and fauna were native to those areas left the young scientist-to-be with a great respect for nature. "I also have one heck of a leaf and rock collection," she laughs.

Most importantly, Nickerson credits her family for not biasing her decision-making or career choices.

"They wanted me to choose a career that made me happy in life and to be the best that I could be at it," Nickerson recalls. "They told me that there was nothing that I couldn't do in life. They never placed limitations on my creative abilities, either in or out of the classroom."

The ASU scientist has gone on to develop a multitude of interests. She is an avid sports car enthusiast, participates in team sports, does strength training, and collects antiques. But it is science that provides her with the thrill of discovery.

"There is nothing else like it," she says. "Finding something new that no one else has found—that is just so exciting!"

Nickerson claims that research is what she "lives, sleeps and eats for." She sees the possibility of "providing a piece of the puzzle to advance human health."

Cheryl Nickerson

Four studies designed by Nickerson and her colleagues have now flown on the Space Shuttle and the International Space Station. The most recent experiment went up on Atlantis Shuttle Flight STS-115 (12A) in September 2006. Tests were conducted on four microorganisms, including Salmonella, a common pathogen that causes food poisoning.

"Our results show that space flight changes the disease-causing potential of some pathogens. For example, it made Salmonella better able to cause infectious disease. And it caused problems at lower doses. In other words, it became a more potent pathogen," Nickerson says.

The finding is important. The combination of an immunocompromised astronaut with a pathogen that is more virulent could have a significantly negative impact on crew health and mission success.

"In addition, we found that spaceflight globally alters the gene expression profiles of these pathogens as well as their cellular structure," Nickerson explains. The group also identified a likely master regulator involved in the response of these cells to spaceflight.

"This could be an important development," she says. "We want to better understand at the molecular level how spaceflight affects the biology of living cells, both microbial and human. We also want to know how to translate that understanding to the clinical bedside to advance human health on Earth," Nickerson adds.

What changes can make a bad bug worse?

Nickerson has done plenty of ground-based laboratory work. She has shown that Salmonella better resists being killed by stresses relevant to those that it encounters during infection in the host. Those stresses include heat stress—moving from outside to inside the body. Acid stress relates to the condition inside the stomach. Osmotic stress refers to changes in the water and salt concentration.

The presence of macrophages is also important. Macrophages are part of the immune system. They are one of the human body's early defense mechanisms against infection.

Nickerson says that these visible changes are reflected in the altered gene expression profiles of Salmonella during growth in the ground-base RWV bioreactor. They also are seen during true spaceflight. She found alterations in more than 160 genes. Many of those genetic alterations enhance the ability of the bacteria to cause disease.

Nickerson says that understanding the molecular effects of mechanical stressors on living cells is also important. Mechanical force is an important underlying cause for many different kinds of human disease. It can lead to cardiovascular disease, stroke, diabetes, cancer, and osteoporosis.

"We know there is a link between disease and mechanical forces," Nickerson explains. "But we need to know the molecular mechanisms involved. That will help us to develop new ways to treat and prevent disease."

Nickerson's excitement is infectious. The potential impact of her ASU group's findings could advance the prospects for improving human health on a global basis.

"You need to make this world a better place when you leave—no matter what your field is—and hopefully this is what we are doing," says Nickerson.

Will she achieve her goals? Perhaps the Kennedy Space Center bumper sticker on her wall says it best: "Failure is not an option."

Cheryl Nickerson's work is supported by NASA, National Institutes of Health, and the Department of Homeland Security.

Listen to a podcast with the scientist at: http://askabiologist.asu.edu/podcasts/.