New Study Unlocks Superbug Secrets
Sep 20, 2017 Cedars-Sinai Staff
Our immune systems usually have pretty good memories. We get an infection, and the next time our immune cells encounter that particular culprit, they know just how to gear up and fight it.
But one of the world's biggest public health enemies has escaped decades of efforts to create a successful vaccine: Staphlylococcus aureus.
Staphlylococcus aureus (AKA "staph") frequently causes skin infections, but can sometimes lead to deadly conditions such as sepsis, pneumonia, and bloodstream infections. This is especially a problem for patients in the hospital, where their immune systems could already be weakened by other illnesses.
"The study explains why our immune system is fooled by staph."
A new study by Cedars-Sinai investigators shows how staph cells evade the immune system and offers a clearer picture of how a successful vaccine would work.
Creating an effective vaccine has been a priority in the medical community, and for good reason: One strain of staph, the superbug Methicillin-resistant Staphylococcus aureus, or MRSA, is considered one of the top drug-resistant threats in the US, causing more than 11,000 deaths per year according to the Centers for Disease Control. The superbug kills more Americans than HIV.
"Widespread MRSA infections have prompted routine use of once last-line antibiotics, and this is making the antibiotic resistance problem worse," says Dr. George Liu, co-lead author of the study and a pediatric infectious diseases physician at Cedars-Sinai's Maxine Dunitz Children's Health Center and the F. Widjaja Inflammatory Bowel and Immunobiology Research Institute.
No matter how many times a body suffers a bout of staph infection, the immune system never seems to "remember" how to fight off the disease. How does staph keep winning against the body? By strengthening its own cell walls, effectively hiding the molecules that would tip off the immune system and trigger the body to fight back.
"Essentially, staph tricks the body's T cells, which are white blood cells that fight infection, and prevents them from mounting an effective defense," says co-lead author Gislaine Martins, PhD, a research scientist at the F. Widjaja Inflammatory Bowel and Immunobiology Research Institute.
"Essentially, staph tricks the body's T cells and prevents them from mounting an effective defense."
As a result, the body does not develop long-term immunity and remains vulnerable to that particular staph infection throughout life.
"The study explains why our immune system is fooled by staph," says Martins. "Staph evolved to have this design that makes this modification in its cell wall. It can't be degraded into a million little pieces and properly detected by the immune system, which won't remember the bacteria the next time the body is infected."
When the research team removed the cell wall modification, the staph cells spilled their molecules more easily. Laboratory mice exposed to the modified bacteria were able to develop a memory immune response and were protected from repeat infections.
The study provides clues of what type of element could be added to staph vaccines to make them more effective. Most staph vaccines have tried to stimulate the production of antibodies—specialized molecules that recognize foreign bodies and mobilize the immune system—but this study suggests that a successful vaccine should harness the body's T cells.
The study appears in Cell Host & Microbe.
Funding for this work was provided by NIH research grants R01AI103542, R21AI083948 and R01AI127406 and by the F. Widjaja Foundation IBIRI Institute, Cedars-Sinai Medical Center.