The University of Nebraska Medical Center has received $11.8 million over five years to continue research on four projects targeting one of the most difficult to treat infections – those caused by methicillin-resistant Staphylococcus aureus (MRSA). The cumulative total of the grant, which was first funded in 2009 by the National Institutes of Health National Institute of Allergy and Infectious Diseases, will be $31 million by the end of 2024.
“We’re learning really interesting details about how bacteria colonize the skin surface and use the nutrients available to them within a human,” said Ken Bayles, Ph.D., principal investigator of the program project grant and director of the UNMC Center for Staphylococcal Research (CSR). “They need nutrition so they’ve adapted to the human host. We have a better understanding of what the bacteria are eating, so we can find ways to eliminate them.
“The bacteria are sophisticated – much more sophisticated than we imagined. We’ve also identified new biofilm targets that are critical for escape to overcome the immune system – it’s a battle. The immune system has evolved to respond to infections, but the staph bacteria have developed many ways to evade, or even prevent a normal response. By learning how staph can cause infection, we can figure out strategies to overcome infection.”
More than 119,000 people suffered from staph infections in the United States in 2017 – and nearly 20,000 died, according to a report released recently by the Centers for Disease Control and Prevention. Between 2012-2017, there was an increase of 3.9% in community-onset staph infections.
The CSR also has produced a “mutant library” – genetic tools researchers around the world can use in their research. At international conferences, like a recent one in Spain, researchers in their presentations frequently mention the Nebraska tools they use in their research. “It helps enhance our own research while providing valuable tools others can use to advance their research,” Dr. Bayles said.
One of the health areas of concern involves patients who have joint replacement surgery. Infections can occur in about 1% to 2% of these patients. Considering about 1 million total joint replacements are performed annually and the number is expected to rise to more than 4 million by 2030, new prevention and treatment discoveries are urgently needed.
“As we become more sophisticated in the clinical setting doing more artificial hips, knees and shoulders, as well as install other devices, they all present opportunities for staph to colonize,” Dr. Bayles said.
“This grant is the foundation of our center for staph research,” he said. “We take the designation very serious. We also put on a workshop every year. Students come here from all over. If you want to know about staph, this is the place to be.”
Additional quotes:
“My laboratory is centered on understanding how Staphylococcus aureus biofilms are able to escape detection by the immune system to cause chronic infections. This is pertinent to medical device-related infections, such as those associated with artificial hips and knees. Our work has demonstrated that S. aureus co-opts the immune response to promote anti-inflammatory responses that are not effective at killing bacteria. We have shown that we can re-program this defective immune response to improve bacterial killing and limit infection. We will continue to focus on identifying new ways to improve immune recognition of S. aureus that will hopefully lead to new treatment strategies.”
Tammy Kielian, Ph.D., professor of pathology, Department of Pathology/Microbiology and Choudari Kommineni, D.V.M., Ph.D., Professor of Pathology
“My laboratory is focused on understanding how Staphylococcus aureus grows, survives and persists within infections. Specifically, what particular nutrients it acquires from humans during various types of infections. This work allows us to more fully understand how it has co-evolved with humans to co-exist in most cases but in other cases cause devastating disease.”
Paul Fey, Ph.D., associate director, professor and vice chair, Department of Pathology/Microbiology
"The metabolic landscape of Staphylococcus aureus is incredibly versatile and allows it to adapt quickly to changing environments. It is fundamental to this pathogens’ ability to colonize and persist within the human host. The work by my group focuses on understanding the metabolic strategies utilized by S. aureus to optimize its fitness in response to biological stress. Our studies will enable the characterization of key metabolic nodes that are crucial to staphylococcal pathogenesis."
Vinai Chittezham Thomas, Ph.D., assistant professor and research scientist, Department of Pathology/Microbiology
“My laboratory is focused on how Staphylococcus aureus regulates community behavior during infections. In chronic medical-device infections, we are investigating the mechanisms used by S. aureus to form biofilms on these devices and how this pathogen regulates dissemination from devices to other body sites. Our goal is to identify ways to intervene in these mechanisms in order to better treat S. aureus infections.”
Alexander Horswill, Ph.D., professor of Immunology & Microbiology, Department of Immunology and Microbiology, University of Colorado
$11.8 million grant funds continued discovery on staphylococcus infections
