A single gene called cylE within the important bacterial pathogen Group B Streptococcus (GBS), controls two factors that act together as a “sword” and “shield” to protect the bacteria from the killing effects of the immune system’s white blood cells, according to researchers at the University of California, San Diego (UCSD) School of Medicine.
GBS is the leading cause of serious bacterial infections such as meningitis and pneumonia in newborns and is increasingly recognized as a serious pathogen in adult populations, including the elderly, pregnant women and diabetics.
In studies with mice and human blood samples, published in the online edition of Proceedings of the National Academy of Sciences the week of September 20, 2004, the UCSD scientists demonstrated the protective roles of two cylE-encoded factors, one that creates the unusual orange pigmentation of GBS, and another that produces a toxin called hemolysin that kills immune system cells as they surround and attack the bacteria. These findings could lead to new therapeutic approaches that disarm the bacteria and allow the immune system to do its work.
"A crucial part of the body's defense against bacterial pathogens are white blood cells known as neutrophils and macrophages, which are able to engulf and kill most bacteria" said lead author George Liu, M.D., Ph.D., a UCSD research fellow in pediatric infectious diseases. "We predicted that the GBS bacteria had a unique ability to avoid the killing by white blood cells."
This unique ability turned out to include both the killing effects of the hemolysin toxin, and previously unrecognized antioxidant properties of the GBS orange pigment.
A major weapon that white blood cells use to kill bacteria after engulfment is the production of lethal oxidants similar to peroxide and bleach. Interestingly, the cylE-dependent orange pigment belongs to the family of carotenoids, similar to the compounds that give color to vegetables such as tomatoes and carrots. The anitoxidant properties of food carotenoids have long been touted for their potential health benefits against aging, heart disease and cancer.
“Just as colorful vegetables with antioxidants are touted for their ability to protect us against aging or cancer, we discovered that the GBS bacteria is pulling the same trick to protect itself against our immune system,” said the study’s senior author, Victor Nizet, M.D., associate professor, UCSD Division of Infectious Diseases, and an attending physician at Children’s Hospital San Diego.
The UCSD experiments confirmed the importance of the antioxidant role of the orange pigment, as mutant GBS without the cylE gene was 10 to 10,000 times more susceptible to white blood cell oxidants than the disease producing strain.