Earth Sciences Professor Steven Lower’s new five-year grant of just over $3 million dollars ($3,002,203) from the National Institutes of Health (NIH) will allow him to continue his innovative, cross-disciplinary research on the potentially deadly blood infection caused by bacterial cells that attach to implanted cardiac devices. This affects approximately four percent of the one million patients receiving these implants each year.

This, along with two other recent grants, funds Lower’s long-term, ongoing study of how Staph can attach itself to implanted cardiac devices that then cause sometimes deadly bacterial infections, and support his quest to find ways to prevent this.

The first question people sometimes ask, though, is “How does an Earth scientist get involved with research that seems to be medical in nature?” The quick answer is that Lower’s graduate work spanned several disciplines. “My PhD committee consisted of a biochemist, a microbiologist, an engineer, an aqueous geochemist and a mineralogist; it was a challenge to make that work, but we did,” Lower said.

“It is a bit difficult to put me in a specific category. Maybe I should say that I do nanoscience—that’s a big buzzword right now—it’s a scientific discipline defined by size, basically just the study of small things and is truly interdisciplinary as there are small things everywhere!

“When you look at the world through the eyes, so to speak, of a tiny bacterium, there is no real difference in how the bacterium binds to pebbles in a flowing stream and how a bacterium interacts with implants in the bloodstream,” Lower said. “Bacteria like to live on surfaces, whether it’s a pebble or a prosthesis, they have no constraints; they’re happy to call either place home. “If you truly want to investigate them, you have to cross disciplines. Bacteria don’t read textbooks. They are unencumbered by what we humans may define as the realm of medicine or geology.

“And, if you want to find out how they live in the environment and how they interact with minerals, you have to know both mineralogy and microbiology.”

Lower has been doing this work for almost 10 years, leading a project that is a true international, multi-disciplinary collaboration with medical researcher, Vance Fowler, at Duke University Medical School; biochemist Magnus Hook at Texas A&M Medical campus; geneticist Lauren McIntyre from the University of Florida; Professor Roberto Lins, a computational chemist in Brazil; medical doctor Yok-Ai-Que from Switzerland; and a very talented Ohio State post-doc named Nadia Casillas-Ituarte, who has been working in Lower’s lab for the past few years.

In 2002, Lower was invited to give a talk at Duke and the rest—as they say—is history. He and Fowler have been working together ever since.

“First, we had to learn each other’s lingo,” Lower said. “That in itself was a project, but well worth it.”

Now, they have produced a number of papers together and their students travel back and forth to work in each other’s labs.

In the beginning, their challenge was to figure out why some patients get these infections and some do not. What they found was that those infected patients host strains of the bacteria, Staphylococcus aureus, whose surface proteins have genetic mutations that make them more likely to form a biofilm. This allows them to stick to the surface of the devices, literally, like superglue.

Because biofilms resist antibiotics, the only viable treatment is to undergo surgery to remove the contaminated device and implant a new one. This adds up to thousands of surgeries and racks up more than $1 billion in health care costs every year, not to mention the risk to the patient in having an additional surgery.

Using Staph cells collected from patients – some with cardiac device-related infections – Lower and his colleagues used atomic-force microscopy and powerful computer simulations to determine how Staph bacteria bond to the devices in the process of forming these biofilms.

They found a bond forms when a protein on the bacterial cell-surface connects with a common human blood protein coating an implanted device.

This discovery offers clues about potential techniques that could be used to prevent infections.

“In the past, we focused on one Staph gene that makes a receptor that can bind to one protein,” Lower said.

“But, there are many other genes and virulence factors; we predict there are small changes in the organism’s genome. Our new grant will allow us to sequence the entire genome, using samples we get from patients with implants.  

“My colleague has been collecting samples of Staph—5,000 approximately—and putting them in the freezer for 20 years. Out of all of these, a small percentage have these mutations, which translates to patients developing infections.”

While the percentage is small, the problem is not. Each year more and more folks get implants and it’s not just cardiac implants that can be affected.

“We also are looking at hip and knee replacement to see what might be happening there. We have to remember, bacteria like to live on surfaces, including human surfaces. The human body contains probably 10 times more microbial cells than human cells. Typically, that is not a problem—the microbes live in a commensal, symbiotic relationship with their hosts—but sometimes bacteria growth on human surfaces can be serious.

“So, our goal is still to stop the cell from binding; we’re going back to that first step, to take a close look at how it binds, then maybe we can figure out how to interrupt or stop it. If a Staph bacterium cannot bind to an implanted surface then absolutely no biofilm infection can form.

“These collaborations across disciplines are not easy; you need patience and persistence to make them happen. Fortunately, for us, some funding agencies, like NSF and now NIH are realizing the need to fund such interfaces between disciplines like microbiology and geology that are engaged in potentially transformative, high-risk, high-reward work.”

—Sandi Rutkowski