Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Staphylococcus aureus bacteria turns immune system against itself

20.11.2013
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. aureus—the 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 mutations—to the staphylococcal nuclease (nuc) and adenosine synthase A (adsA) genes respectively—were 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."

The study, "Staphylococcus aureus Degrades Neutrophil Extracellular Traps to Promote Immune Cell Death," was supported the National Institute of Allergy and Infectious Diseases and the American Heart Association. Additional authors include Vilasack Thammavongsa and Dominique M. Missiakas

Kevin Jiang | EurekAlert!
Further information:
http://www.uchospitals.edu

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>