UNC Health Talk

Breaking Down Bacteria

A college education. That’s as far as the imagination of Rita Tamayo’s parents could take them while raising their daughter in Houston, Texas. They had no idea she’d become a scientist at one of the top research universities in the country. Tamayo herself had no idea. She was an artsy craftsy kid, big into drawing and painting through childhood and into college. And then she discovered the wild world of microbes. She never looked back.

Tamayo, now an assistant professor in the department of microbiology and immunology, is trying to understand the inner workings of two tough bacteria – Vibrio cholerae and Clostridium difficile. For her research acumen and dedication as a role model for aspiring scientists, she was named a Simmons Scholar by the UNC School of Medicine.

We sat down with Dr. Tamayo to ask her about her becoming a scientist, her research, and those two pesky pathogens that cause disease in just about every country on the planet.

Why did you choose to study biology at Rice and what led you to pursue a career as a researcher in the field of microbiology and immunology?

When I was in high school, I was focused on finding a university that had good science programs and a good art department because I intended to be an art and chemistry double-major. I had an art background and I had a great high school chemistry teacher who taught the material in a really fun and exciting way.

But the more I learned more about science, the more I liked biology. Microbiology wasn’t even on my radar at that point, but as things progressed I discovered it.

Microbes and pathogens, in particular, are just really interesting to me – how are they able to cause disease and how is that disease counteracted by a person’s immune system? As I gained a better understanding of science I also gained experience on the research side of things – the day-to-day of academic research. That’s what I really fell in love with – the research process. And microbiology seemed like the most fun venue.

I find there’s a lot of creativity and problem solving involved. Science is not just about understanding what’s already known; it’s about pushing what’s known a little bit further. And I think the creative process is a really big part of that.

At Rice, I was really close to getting an art degree but I could never get into the art history classes because they always conflicted with labs. So that didn’t work out.

You study Vibrio cholerae and Clostridium difficile. What are they and why is it important to investigate them?

These are two intestinal pathogens. My training is in Vibrio cholerae. Clostridium difficile is something we’ve started studying more recently. What they have in common is that they both produce toxins that cause intestinal disease. Other than that they’re actually pretty different.

Vibrio cholerae causes the disease cholera, which is a really profuse diarrheal disease, and it’s a big problem in developing countries with poor access to clean drinking water. The outbreak in Haiti a couple years ago is a recent example of cholera being a big problem.

Clostridium difficile (or C. diff, as it’s often called) is a bigger problem in developed countries – the United States, Canada, Australia, and European countries, in particular – because C. diff infections are usually a consequence of antibiotic use for treating other infections, and these countries are heavy antibiotic-users. If people are taking antibiotics that affect their normal gut bacteria, then that makes people susceptible to C. diff. So, this is a major problem for hospitals and nursing homes.

There are thousands of deaths a year associated with C. diff infections, and the cost of treating these infections is upwards of $2 billion to $3 billion dollars in the U.S. alone.

From a scientific perspective, C. diff is a really fascinating organism. It forms spores, which are basically these dormant cells that are resistant to just about every kind of standard disinfectant you can throw at it except bleach and special spore-killing disinfectants. Things like hand sanitizers really don’t work on C. diff spores very well.

So, in hospitals, for instance, people with C. diff can shed spores and expose the next susceptible person. It can then grow in the intestine and cause disease.

What is c-di-GMP and what role does it play in these pathogens?

That’s the shorthand name of the molecule cyclic diguanylate.

Bacteria have lots of ways of sensing their environment and then adapting to it. Cyclic diguanylate is one molecule that bacteria use to adapt to different conditions in their environment. This small molecule inside a bacterial cell mediates information from the cell surface to targets inside the cell so that bacteria can change their behavior.

The common thing that cyclic diguanylate regulates is whether bacterium stays put or moves someplace else in search of better food or to avoid something that’s bad for it. But my lab and others have found that it plays another role in human disease. We’re trying to understand that role.

Since joining UNC in 2009, what progress have you made?

On the Vibrio cholerae side, that organism is really easy to genetically manipulate. So we can ask some pretty detailed mechanistic questions about how cyclic diguanylate works in that organism. We’re focused on understanding specifically how the bacterium – the insides of it – can sense changes in cyclic diguanylate and how that translates into bacterial behavior.

I think our biggest strides have been with Clostridium difficile, which we started researching about three years ago. Since then we’ve determined that cyclic diguanylate doesn’t just regulate the bacterium’s motility. It also affects the production of two toxins that are essential for Clostridium difficile to cause disease. They’re called, creatively, toxin A and toxin B.

We’re now starting to explore what else cyclic diguanylate regulates in Clostridium difficile. We know from other studies that different bacterial species coopt this cyclic di-guanylate signal to regulate a lot of different processes. So we want to know if there is anything new to discover about cyclic diguanylate in Clostridium difficile, anything that’s unique to it.

The end goal is to understand enough about the organism and how it causes disease to be able to circumvent what it does to be virulent. For example, knowing that cyclic diguanylate regulates toxin production means we can try to target the enzymes that produce or degrade cyclic diguanylate in a way that would prevent the production of toxins.

This sort of basic science takes a long time and a lot of dedication over many years; what’s the most rewarding part of this sort of work?

I think the reason why I find it so rewarding is that I actually like the day-to-day of being in a lab working with my trainees and my colleagues. I’m able to appreciate the process. I can celebrate the small successes and get past the regular failures inherent to basic science research. Also, the fact that I really do have fantastic students and post docs that I get to work with every day, seeing them develop their own ideas and hypotheses and testing them, I find all of that really rewarding.

The UNC School of Medicine Simmons Scholar Program, established in 1994 by UNC School of Medicine Dean Michael Simmons, provides salary support for talented and diverse faculty members, as well as junior faculty who serve as role models.

Media Contact: Mark Derewicz, 919.923.0959, mark.derewicz@unch.unc.edu