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August 30, 2014

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Big things are happening at UNLV regarding small invaders

Professors leading research that is proving microbes are an essential part of human existence

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Leila Navidi

In these tubes are tiny honeybee larvae that UNLV grad student Israel Alvarado is testing with chemical compounds that may block the germination of Paenibacillus larvae, the bacteria that causes American foulbrood.

Inside the Microbiome

Tom Schoenfeld, vice president of Wisconsin-based biotech company Lucigen, is also something of a bio-prospector. In collaboration with UNLV associate professor and microbial ecologist Brian Hedlund, Schoenfeld hunts hot springs for Launch slideshow »

At a coffee shop near UNLV, the discussion turns from alien movies to poker chips to theories on the origin of life. The common thread: microbes, invisible organisms that share our planet — and our bodies — in ways both threatening and essential.

I am a germophobe. Not anywhere near the league of Howard Hughes and his Mason jars, but you couldn’t pay me to eat nachos after bowling a few frames. Given the glut of scare-tactic commercials for kitchen wipes and headlines about salmonella in bagged salad and flesh-eating bacteria in a Georgia river, it’s hard not to overreact. Even the content for grade-schoolers on kidshealth.org characterizes microbes primarily as “tiny invaders.”

Brian Hedlund agrees there are real threats (and that hand washing is wise), but he politely points out that I’m missing the big picture — the huge picture — starting with the fact that the bagel in my hand would be a lot harder to digest without the bacteria in my gut. Our invisible tenants make up the microbiome, a dynamic ecosystem still in the process of being mapped by a National Institutes of Health initiative called the Human Microbiome Project. It sounds familiar because it’s an extension of the Human Genome Project, a 13-year undertaking that sequenced the 3 billion chemical base pairs that constitute human DNA and identified more than 20,000 genes within it.

Hedlund says that, in a sense, our genome isn’t complete without our microbes. And the more we understand about the “uneasy truce” that allows us to coexist, the better we’ll understand the mechanics of our own inner workings, from how they developed to how they might be manipulated to our advantage.

Hedlund is an associate professor at UNLV, a microbial ecologist who stalks hot springs across the Great Basin in search of “biological dark matter.” He’s one of a handful of researchers across the university exploring the many layers of the microbiome in hopes of finding ways to harness its energy and unique capabilities as well as to minimize its potential for harm. Despite the latter, Hedlund doesn’t like the word “germ.”

The connotation has contributed to large-scale industrial, medical and personal practices that are encouraging resistance in organisms we should legitimately fear. We overuse antibiotics on our food and misuse them on ourselves. We zealously (and fruitlessly) try to sterilize our skin and everything it touches. In our blanket defense against the tiny invaders, we force them to adapt and potentially become more lethal. And the ironic reality is that no matter what soap I use, living in this crazy, dirty world comes with some risk.

•••

Las Vegas is a perfect microcosm. All day, every day, people come and go from every corner of the world. They shake hands, share drinks, push chips on the felt and buttons on the slots, maybe even make out with a stranger in the back of a cab. This city encourages contact, not to mention activities that weaken the immune system. So, just like the armpit it has been likened to, Vegas offers an ideal climate for the greatest diversity of microbes to get busy.

Weekly editor Sarah Feldberg ran this theory by Dennis Pirages, a UNLV political science professor and authority on globalization and pandemics, when outbreak blockbuster “Contagion” hit theaters last fall.

“It only takes 24 hours for a disease to spread from Southern Europe to Las Vegas,” Pirages said. “I hate to think of a poker chip as a wonderful way to pass a virus, but ...”

Thanks to Hedlund and Bluff magazine, we have an idea of what’s hitching a ride on the Strip’s chips. The magazine approached Hedlund in 2007 about doing a lighthearted sting on local casinos, and he and his students were game. In a single day, the research team fanned out to five properties, buying $5 stacks of $1 chips and “doggy-bagging” with sterile gloves and Ziplocs. Hedlund laughs at the memory, mostly because none of the casino employees batted an eye.

“I didn’t expect any pattern,” he said. “I thought it would just be random, but I was really surprised to see that this one company had significantly less microbes on their chips.”

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A competitor plays with his chips during play at the 2011 World Series of Poker Friday, July 15, 2011.

That company was the only one named in Bluff’s article — the Wynn. On the other end of the spectrum, “Casino No. 3” had one chip carrying more than 5,600 microbes and averaged nearly 3,000 per chip, mostly Staphylococcus and Bacillus. Staph is commonly found on skin, but some forms cause serious infections and one is related to drug-resistant MRSA, though Hedlund’s team didn’t detect it. The Bacillus cereus they did find is known to cause food poisoning. Sounds gross, until he reminds you that one of your hands is home to about 100 billion bacteria (with some fungi thrown in for color). Most are either helpful or harmless, provided your immune system is up to snuff.

But these are not the elusive biological dark matter. The life forms Hedlund hunts are rare, require accommodations hot enough to hard-boil a human and are nearly impossible to grow in the lab — three reasons most have never been scientifically described (though it’s worth noting that 75 percent of all major microbial lineages have yet to be studied, even though they comprise the bulk of our planet’s biodiversity). That represents an enormous genetic reservoir, and with major funding from the National Science Foundation, NASA and the U.S. Department of Energy, Hedlund is determined to tap it.

“My angle is to look into finding better microbes that have better enzymes to degrade this stuff. The weeds are being grown, but they’re currently not good enough,” he said, referring to the cellulose-digesting enzymes already used by the biofuel industry, which come from microbes that are easily found, easily grown and probably not the best at what they do. In that vein, Hedlund is also partnering with a Wisconsin-based biotech company, Lucigen, to identify heat-loving viruses with enzymes involved in nucleic acid (DNA and RNA) processing that have the potential to improve forensic and medical diagnostics. Not bad for a bunch of germs.

“It is this world you can’t just casually see and understand something about,” Hedlund said. “Being in microbiology, my eyes are open to more.”

•••

Serendipity is hardly the first word that comes to mind when you see an image of 9/11. Yet, had Ernesto Abel-Santos not moved to New York City a month before the attack and ensuing anthrax scare, he might never have chased that pathogen and others that threaten human health.

Originally from the Dominican Republic, Abel-Santos jokes that he was kicked out of the country because he couldn’t play baseball. While the professor’s research in UNLV’s Department of Chemistry deals with serious biohazards, his sense of humor about life and microbes is finely tuned.

When I ask if pathogens, the agents of infectious disease, look evil under a microscope, he says in his dead-on Antonio Banderas baritone, “Let me show you.” The next second, I’m face-to-face with plush toys modeled after anthrax and Clostridium difficile. Lucky for us, Abel-Santos says, the threat of anthrax-related bioterrorism is small because it’s really hard to make into an airborne powder without killing yourself.

C. diff, on the other hand, is a disease of hospital patients — an unwitting creation of modern medicine. Antibiotics that blast bad microbes also blast good ones that keep common invaders like C. diff from germinating. Free to come out of hibernation and roam, the bacteria cause flu-like symptoms, violent diarrhea and about 50,000 deaths in the U.S. every year.

“This is an infection that recurs when you’re taking antibiotics. So they have to give you even stronger antibiotics. But the problem is that you’re still killing your flora,” Abel-Santos says of the beneficial microbial communities that live in our digestive systems and, as it turns out, are as unique as we are.

To restore balance, some desperate patients try “fecal transplantation,” essentially consuming a healthy donor’s fecal matter (or having it inserted from the other end) in order to repopulate their systems. Chronic sufferers will be keen to know about a paper Abel-Santos recently submitted for publication, detailing the creation of patent-pending compounds that keep C. diff spores on lockdown. It’s the result of years of painstaking tests to determine the triggers of germination and then chemically disable them.

“What we expect these compounds to do is basically serve as a flora surrogate,” he said. “It’s not going to cure the disease. The idea is to prevent the disease.”

Another Abel-Santos project addresses American foulbrood, a highly contagious bacterial infection known to wipe out honeybee larvae. It’s a big problem for agriculture worldwide because honeybees pollinate crops, and if their colonies are devastated, so is our food supply.

UNLV doctoral student and bee whisperer Israel Alvarado is on the case, and he has already found the triggers and some inhibitors of American foulbrood’s culprit, Paenibacillus larvae. Now he’s preparing to test them on rows of tiny honeybee larvae from the hives just outside the life sciences building, but he and Abel-Santos aren’t just looking to block germination.

They’re also targeting ways to encourage it because, in spore form, bacteria are impervious to pretty much everything — chlorine, heat, antibiotics — and they can lie in wait for tens of millions of years. Making them germinate also makes them vulnerable enough to kill, so the usual bonfire of contaminated beekeeping materials wouldn’t be necessary. Sometimes, preventing disease means tickling the monster.

Like Ridley Scott’s subconscious, this is too creepy. But Abel-Santos puts things in perspective by telling me about the failure of biosafety detectors.

“They work great in the lab, but they’re so sensitive that they’re false alarms. They trigger with everything,” he said, “because spores are everywhere.”

•••

The beauty of mother nature is that’s she’s fair. As Penny Amy says, all major life forms have their own viruses. Amy is a UNLV microbiology professor, and she’s working with Abel-Santos and two other faculty members on a three-pronged solution to American foulbrood, funded by a sizable grant from the USDA. Her approach is to infect the thing that infects the bees. I ask what P. larvae does to the infant insects, and she calmly replies that it dissolves them from the inside out.

The answer is as simple as finding the right virus, or phage. But Amy says there had been two reports of such a virus, ever, and both were decades ago in Eastern Europe.

“We had no idea where the phage were, if they were active and if we could use them. So we decided to go find them,” Amy said. “We tested 98 samples — soil in and around beehives, wax, honey, dead bees, flowers, and then one day I said, ‘I wonder if Burt’s Bees products have them.’”

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It may not be immediately clear how our lives are affected by the lives of honeybees and the organisms that harm them, but many of the alarming headlines of today have roots in upsets to the natural balance of things.

UNLV master’s student Diane Yost found an abandoned Burt’s Bees lip balm under a park bench that day, and sure enough, of the 98 samples, 31 (including the lip balm) were positive. Amy was blown away. She and Yost have since tested all of them on eight strains of P. larvae.

Based on the patterns in the “zones of death” on their Petri dishes, a particular phage, H1P, is the microbe to beat. It’s effective on all eight strains, though Amy and Yost continue to search for candidates even better at wiping out the honeybee scourge. Once identified, several could be cloned and made into a cocktail that could be sprayed in the hive or fed to the larvae, bridging the gap to the natural immunity that comes with adulthood. And they’re looking at harnessing the power of a viral enzyme called lysin that ruptures bacterial cell walls.

You might think it’s a lot of sweat over some lousy bees, but you’d be missing the huge picture. That’s what Amy tries to impress upon her students, especially those going into the health care field and those only taking biology because it’s a requirement.

“Life began with microbes. I believe life will end with microbes, if it ever ends. They are more numerous than anything on Earth. They are more adaptable than anything on Earth. They live in every single niche,” she said. “They invented every kind of metabolism that there is on Earth to this point, and other organisms made use of it. We have nearly the same metabolism as E. coli, and E. coli has been around a lot longer than we have.”

Funny how thinking about the smallest creatures makes me feel small. Because right now, there are tiny living things clearing my skin of residue, making vitamins that enable my blood to clot and keeping lids on those renegade intestinal spores. We need each other.

A version of this story was first published in Las Vegas Weekly, a sister publication of the Sun.

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