Bio Nebraska

UNMC staph research team lands $11.1 million grant to investigate MRSA

(July 16, 2009) A University of Nebraska Medical Center research team specializing in staph infections has landed an $11.1 million program project grant to study one of this country’s most dangerous bacterial pathogens – community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).

The grant was awarded by the National Institutes of Health (NIH). It is the largest research grant ever awarded to UNMC’s department of pathology/microbiology and is the only program project grant given by the NIH to investigate MRSA.

The research team is headed by Ken Bayles, Ph.D., professor of pathology/microbiology and the investigator who previously made a breakthrough discovery dealing with bacterial programmed cell death.

The research team, a powerhouse of basic science and clinical experts who are focused on hospital-induced infections, is going after CA-MRSA, which has become resistant to most standard antibiotics and is becoming more resistant to newer ones. Researchers have nicknamed it the “superbug.”

Thomas H. Rosenquist, Ph.D. vice chancellor for research and professor of genetics, cell biology and anatomy, said only the most well-recognized, interactive, productive senior scientists are able to put together and manage the kind of large-scale projects that merit the multi-million dollars that come with a program project grant.

“Dr Bayles is all of the above,” he said. “This innovative and exciting program predicts a major advance in our understanding of MRSA, which is a major health threat.”

The five-year, multi-investigator/multi-institutional grant funds four projects, including three from UNMC which involve investigators from different, yet complimentary areas of expertise. The fourth project continues collaboration with an investigator at the University of Iowa.

The team has expertise in varied aspects of staph including biofilm development, gene regulation, physiology and the immunology of staph infections. The hypothesis to be tested is that staph biofilm formation involves complex developmental processes that affect the host immune response, Dr. Bayles said.

The researchers seek to understand how staph bacteria grow in animals to cause disease – using a mouse model that has genetic variances to test various outcomes. They also will look at the mechanism behind biofilm development – how it forms and becomes resistant to the body’s natural immune response and to antibiotics.

Staphylococcus aureus, which is present on the skin or in the nose of healthy people, is the cause of some of the most common causes of minor skin infections in the United States. It has historically been a leading cause of hospital infections in humans worldwide. In the past several decades, the emergence of MRSA, which is resistant to multiple antibiotics, has left relatively few therapeutic options available.

Staph causes 1.7 million infections and approximately 100,000 deaths each year in the United States. Surgical sites and the bloodstream are common targets, but it also causes pneumonia. Catheters, pacemakers and any implant device, such as hip and knee replacements, are prone to infection. Bloodstream infections are a leading cause of death in the United States.

Currently, about 50 to 60 percent of staph infections are resistant to multiple kinds of antibiotics, making staph much more difficult to treat. Not only are hospital-acquired MRSA infections on the rise, but so are MRSA infections in those living in the community. Today, these strains now pose a serious public health threat, causing more deaths per year than HIV-AIDS.

“Now, healthy young people are getting staph infections and develop complications that, in some cases, can lead to death,” Dr. Bayles said.

“It’s because this new strain of MRSA, which was first identified about four years ago, is not only resistant to methicillin but also has a lethal combination of virulent traits. Unfortunately, it’s not clear why this strain is so deadly.”

Over the past decade, health care surveillance officials have seen a remarkable increase in resistance among community- and hospital-acquired pathogens that were routinely susceptible to such antibiotics as penicillin, methicillin and vancomycin, a traditional drug of "last resort.”

UNMC is the only public health science center in the state. Its educational programs are responsible for training more health professionals practicing in Nebraska than any other institution. Through their commitment to education, research, patient care and outreach, UNMC and its hospital partner, The Nebraska Medical Center, have established themselves as one of the country's leading centers in cancer, transplantation biology, bioterrorism preparedness, neurodegenerative diseases, cardiovascular diseases, genetics, biomedical technology and ophthalmology. UNMC’s research funding from external sources now exceeds $82 million annually and has resulted in the creation of more than 2,600 highly skilled jobs in the state. UNMC's physician practice group, UNMC Physicians, includes 513 physicians in 50 specialties and subspecialties who practice primarily in The Nebraska Medical Center. For more information, go to UNMC’s Web site at www.unmc.edu.

Meet the team

Co-investigators at UNMC are Paul Dunman, Ph.D., assistant professor of pathology and microbiology, and Mark Rupp, M.D., professor of infectious diseases.
The grant also funds more than $1 million in state-of-art equipment for a biofilm growth and analysis and a bioimaging core laboratory. Researchers funded by the grant and their projects are:

Dr. Bayles, who is a native of Hutchinson, Kan., is studying regulated cell death during biofilm development;
Paul Fey, Ph.D., a native of Garden City, Kan., and an associate professor and associate director, pathology/microbiology, is studying the metabolic changes important for biofilm formation in staph;
A native of Stanton, Neb., Tammy Kielian, Ph.D., associate professor, pathology/microbiology, is studying the innate immunity to staph biofilm; and
Alex Horswill, Ph.D., assistant professor, microbiology, University of Iowa, is studying enzymes and nucleic acids involved in biofilm development and disease.