The Infectious and Tropical Disease Institute (ITDI) has a strong track record in research aimed at understanding and preventing the spread of particular tropical diseases such as Chagas. But ITDI has recently created a new research group, with a broader focus – to gain a better understanding of how disease-causing bacteria of different kinds survive inside their human hosts.
The new group, the Bacterial Pathogenesis Initiative (BPI), brings together three OHIO researchers from different backgrounds to share and develop knowledge on bacterial pathogenesis – the process by which bacteria infect and cause disease in a host. Understanding how this process works can help scientists find new treatments, to disrupt the ways in which bacteria adapt to our bodies and make us sick.
The need for such research is especially pressing due in part to the phenomenon of increasing resistance to antibiotics. The number of deaths caused worldwide by infectious diseases has increased over the last 15 years, and one reason is that antibiotics once effective in curing particular infections no longer work as well as they used to, as bacteria adapt to them. New, non-antibiotic treatments are needed that target the mechanisms by which bacteria cause disease within humans. To find them, researchers need a detailed understanding of how bacteria adapt to human bodies at the cellular level.
The BPI is currently made up of three OHIO researchers: Ronan Carroll, Ph.D. assistant professor of biological sciences at OHIO; Erin Murphy, Ph.D., associate professor of bacteriology with the Heritage College of Osteopathic Medicine; and Nathan Weyand, Ph.D., assistant professor of biological sciences at OHIO. In their research, all are looking at new and alternative ways to interfere with bacteria’s ability to live in a human body and cause illness.
Carroll calls the growth of antibiotic resistance “possibly the biggest problem facing medicine in the 21th century. We are facing a scary situation where in one to two decades’ time, a large number of bacterial infections may no longer be treatable by antibiotics. It is certainly a global problem, but for countries like the United States in particular, is even a bigger problem because bacteria resistances are more prevalent here than they are elsewhere.”
One of his current research lines looks at the secretion of toxins by staphylococcus aureus, a bacterium that can cause a host of ills from pneumonia to meningitis. S. aureus manufactures many different toxins inside the human body, which attack human cells. But before they can do so, these toxins must be transported outside the bacteria. If that movement can be arrested, S. aureus could be disarmed of its ability to make us sick.
”What we are interested in looking at is the process whereby the bacteria transport the toxins outside of the bacterial cells,” Carroll explains. “If you could somehow disrupt that process, those toxins are not going to be functional, because they cannot go and find their targets in the human cell.”
Dr. Weyand’s research includes an effort to identify factors that the Neisseria gonorrhea bacterium needs to survive in a living host. “If we determine a list of bacterial factors that we know are required for that process, then perhaps some of them can become vaccine antigens,” he says.
Dr. Murphy works with Shigella, the bacteria that cause shigellosis, a diarrheal disease that leads to the death of around one million people worldwide annually. Much of her work focuses on how these bacteria adapt to different environments. For example, Shigella uses molecular mechanisms known as RNA (ribonucleic acid) thermometers to sense whether it’s inside or outside a body. If that sensing process can be short-circuited, the bacteria won’t know they’re inside a host, and won’t adapt to survive there.
“If we can disrupt the bacteria’s ability to adapt to the environment, then that decreases its ability to survive in such an environment,” she said. She noted, for example, that one form of small RNA tells Shigella to adapt to acid conditions like those in the human stomach. “If we can manipulate that small RNA so it is no longer functional, the bacteria dies.”
Though the three initial researchers in the BPI project work with different organisms, they share a broad focus, and all are excited about the new insights collaboration may spark.
“We all work at really understanding, at the molecular level, what bacteria are doing inside the body to make us sick,” Murphy pointed out.
Carroll said he he looks forward to extending his research through working with ITDI facilities like the Center for Research in Health in Latin America (CISeAL), the state-of-the-art biohazard research facility in Ecuador that opened in June 2016 as a cooperative venture between OHIO and the Pontifical Catholic University of Ecuador (PUCE).
“There are three labs here at Ohio University that are working in bacterial pathogenesis that can be involved in this,” he said. “So I think this is a perfect project for me to trying utilize the ITDI and build up the bacteria pathogenesis angle and be able to use those facilities in Ecuador.”
Weyand predicted that the collaboration will benefit all participants, by bringing multiple perspectives to bear on bacterial pathogenesis.
“It is very important to collaborate because people come with projects from different viewpoints,” he said. “And having multiple people focus on a problem with different perceptions often leads to some type of advancement that is beneficial to everybody involved. People have different levels of expertise in different fields, one person quite frequently can’t do everything.”
The Infectious and Tropical Disease Institute (ITDI) at Ohio University seeks to improve the health status of underserved populations through sustainable research, service and educational initiatives related to infectious diseases. We firmly believe that comprehensive research can only be achieved through multidisciplinary and intercultural collaborations. With this institutional value in mind, throughout our history, we have developed projects in collaboration with other institutions and researchers all around the globe, as well as with ITDI associated researchers, belonging to Ohio University.
We’ve created short videos about some of the researchers involved:
To view Ronan Caroll's video, click on image or go to:
To view Erin Murphy's video, click on image or go to: