Navigation Links
Staphylococcus aureus bacteria turns immune system against itself
Date:11/19/2013

Around 20 percent of all humans are persistently colonized with Staphylococcus aureus bacteria, a leading cause of skin infections and one of the major sources of hospital-acquired infections, including the antibiotic-resistant strain MRSA.

University of Chicago scientists have recently discovered one of the keys to the immense success of S. aureusthe ability to hijack a primary human immune defense mechanism and use it to destroy white blood cells. The study was published Nov 15 in Science.

"These bacteria have endowed themselves with weapons to not only anticipate every immune defense, but turn these immune defenses against the host as well," said Olaf Schneewind, MD, PhD, professor and chair of the Department of Microbiology at the University of Chicago and senior author of the paper.

One of the first lines of defense in the human immune response are neutrophils, a type of white blood cell that ensnares invaders in neutrophil extracellular traps (NETs), a web-like structure of DNA and proteins. Captured bacteria are then destroyed by amoeba-like white blood cells known as macrophages. However, S. aureus infection sites are often marked by an absence of macrophages, indicating the bacteria somehow defend themselves against the immune system.

To reveal how these bacteria circumvent the human immune response, Schneewind and his team screened a series of S. aureus possessing mutations that shut down genes thought to play a role in infection. They looked to see how these mutated bacteria behaved in live tissue, and identified two strains that were unable to avoid macrophage attack. When these mutationsto the staphylococcal nuclease (nuc) and adenosine synthase A (adsA) genes respectivelywere reversed, infection sites were free of macrophages again.

Looking for a mechanism of action, the researchers grew S. aureus in a laboratory dish alongside neutrophils and macrophages. The white blood cells were healthy in this environment and could clear bacteria. But the addition of a chemical to stimulate NET formation triggered macrophage death. Realizing that a toxic product was being generated by S. aureus in response to NETs, the team used high performance liquid chromatography and mass spectrometry techniques to isolate the molecule.

They discovered that S. aureus were converting NETs into 2'-deoxyadenosine (dAdo), a molecule which is toxic to macrophages. This effectively turned NETs into a weapon against the immune system.

"Sooner or later almost every human gets some form of S. aureus infection. Our work describes for the first time the mechanism that these bacteria use to exclude macrophages from infected sites," Schneewind said. "Coupled with previously known mechanisms that suppress the adaptive immune response, the success of these organisms is almost guaranteed."

S. aureus bacteria are found on the skin or in the respiratory tracts of colonized humans and commonly cause skin infections in the form of abscesses or boils. Normally not dangerous, severe issues arise when the bacteria enter the bloodstream, where they can cause diseases such as sepsis and meningitis. Antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA), are difficult to treat and have plagued healthcare systems around the world.

Schneewind and his team hope to leverage their findings toward therapies against S. aureus infections. But both genes and the dAdo molecule are closely related to important human physiological mechanisms, and Schneewind believes targeting these in bacteria, without harming human function, could be difficult.

"In theory you could build inhibitors of these bacterial enzymes or remove them," Schneewind said. "But these are untested waters and the pursuit of such goal requires a lot more study."


'/>"/>

Contact: Kevin Jiang
kevin.jiang@uchospitals.edu
773-795-5227
University of Chicago Medical Center
Source:Eurekalert

Related biology news :

1. Bacteria use lethal cytotoxins to evade antibiotic treatment
2. No peak in sight for evolving bacteria
3. Structure of bacterial nanowire protein hints at secrets of conduction
4. Evidence of 3.5 billion-year-old bacterial ecosystems found in Australia
5. Bacteria may allow animals to send quick, voluminous messages
6. Study shows moms may pass effects of stress to offspring via vaginal bacteria and placenta
7. Changing the conversation -- polymers disrupt bacterial communication
8. How zinc starves lethal bacteria to stop infection
9. Battle against resistant bacteria takes huge leap forward
10. Study links intestinal bacteria to rheumatoid arthritis
11. Biochemists find incomplete protein digestion is a useful thing for some bacteria
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/22/2016)... 2016  The American College of Medical Genetics and Genomics ... as one of the fastest-growing trade shows during the ... Bellagio in Las Vegas . ... growth in each of the following categories: net square feet ... of attendees. The 2015 ACMG Annual Meeting was ranked 23 ...
(Date:6/20/2016)... 2016 Securus Technologies, a leading provider ... public safety, investigation, corrections and monitoring announced that ... has secured the final acceptance by all three ... Access Systems (MAS) installed. Furthermore, Securus will have ... installed by October, 2016. MAS distinguishes between legitimate ...
(Date:6/9/2016)... -- Paris Police Prefecture ... to ensure the safety of people and operations in several ... tournament Teleste, an international technology group specialised in ... that its video security solution will be utilised by ... safety across the country. The system roll-out is scheduled for ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... /PRNewswire/ - FACIT has announced the creation of ... company, Propellon Therapeutics Inc. ("Propellon" or "the Company"), ... portfolio of first-in-class WDR5 inhibitors for the treatment ... represent an exciting class of therapies, possessing the ... cancer patients. Substantial advances have been achieved with ...
(Date:6/23/2016)... Lawrence, MA (PRWEB) , ... June 23, 2016 ... ... the Peel Plate® YM (Yeast and Mold) microbial test has received AOAC Research ... test platform of microbial tests introduced last year,” stated Bob Salter, Vice President ...
(Date:6/23/2016)... , June 23, 2016   EpiBiome , ... secured $1 million in debt financing from Silicon Valley ... up automation and to advance its drug development efforts, ... new facility. "SVB has been an incredible ... the services a traditional bank would provide," said Dr. ...
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case report published ... how a patient who developed lymphedema after being treated for breast cancer benefitted from ... the paradigm for dealing with this debilitating, frequent side effect of cancer treatment. ...
Breaking Biology Technology: