November 21, 2013
Our Immune System May Actually Help Staph Bacteria Thrive: Study
Ranjini Raghunath for redOrbit.com - Your Universe Online
Staphylococcus aureus, one of many strains of bacteria involved in Staph infections, is found in about 20 percent of all humans. Under normal conditions, the bacterium dwells harmlessly in the skin or nasal passages, occasionally causing food poisoning or mild skin infections. When it enters the bloodstream, however, it can be quite deadly, causing life-threatening illnesses such as meningitis or sepsis.
One of the ways the bacterium successfully escapes from the host’s defenses is by turning parts of the body’s immune system into traitors, a new study by University of Chicago microbiologists shows.
When bacteria invade the human body, they are attacked by neutrophils -- white blood cells that form the first line of defense. Neutrophils trap the bacteria in a tangled web of DNA and proteins called Neutrophil Extracellular Traps (NETs).
Cells in the surrounding region become casualties in the fight between the immune system and bacteria, creating pus-filled cavities of bacteria, dead cells and neutrophils called abscesses. As the bacteria remain trapped in these abscesses, macrophages -- another class of immune cells – engulf and kill them.
When the researchers looked closely at the abscesses containing S. aureus, however, macrophages were found to be missing, enabling the bacteria to continue infecting the host. They decided to look more closely at how S. aureus caused the macrophages to disappear from the abscesses.
In one of their experiments, they grew strains of S. aureus in a Petri dish containing neutrophils and macrophages. The bacteria stood no chance and were soon cleared out. When the researchers introduced a chemical stimulating the production of NETs, however, the macrophages promptly went missing. This led the researchers to realize that S. aureus was somehow using the NETs to get rid of the macrophages.
In order to understand this mechanism better, the researchers knocked out different genes in different strains of S. aureus and introduced them into lab mice. Strains that lacked genes responsible for building two specific enzymes (nuclease and adenosine synthase A) were unable to defend themselves against macrophages, the researchers found. When they removed the mutations in these genes, the bacteria went back to their lethal selves.
Further research showed that S. aureus used these enzymes to break down the DNA in the NETs into a molecule called dAdo (deoxyadenosine). dAdo is a toxic molecule that kills macrophages, while causing minimal damage to neutrophils. S. aureus was therefore turning NETs against the body’s immune system, the researchers found.
The study was published on Nov. 15 in Science.
“Our work describes for the first time the mechanism that these bacteria use to exclude macrophages from infected sites,"stated Olaf Schneewind, MD, PhD, microbiology professor at the University of Chicago and senior author of the paper. "Coupled with previously known mechanisms that suppress the adaptive immune response, the success of these organisms is almost guaranteed."
As both the enzyme genes and dAdo are involved in vital body functions in humans, developing a drug that removes the bacteria without harming humans will prove difficult, and requires further research, Schneewind explained.