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:2/3/2016)... 2016 --> ... "Automated Fingerprint Identification System Market by Component (Hardware and ... & Finance, Government, Healthcare, and Transportation) and Geography - ... is expected to be worth USD 8.49 Billion by ... and 2020. The transformation and technology evolution from the ...
(Date:2/2/2016)... 2016 Checkpoint Inhibitors for Cancer – ... Are you interested in the future of cancer ... inhibitors. Visiongain,s report gives those predictions to 2026 ... level. Avoid falling behind in data or ... revenues those emerging cancer therapies can achieve. There ...
(Date:2/1/2016)... 2016  Today, the first day of American Heart ... develop a first of its kind workplace health solution ... In the first application of Watson ... ), and Welltok will create a new offering that ... analytics, delivered on Welltok,s health optimization platform. The effort ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... BERG, a biopharmaceutical company uncovering health ... announced the appointment of Jason Haddock ... Haddock brings to BERG over 20 years of ... senior financial functions at pharmaceutical companies, as well ... Niven R. Narain , BERG,s ...
(Date:2/8/2016)... Feb. 8, 2016 /PRNewswire/ - BIOREM Inc. (TSXV: BRM) ("Biorem" ... ten finalists for clean technology companies in the TSX Venture ... 10 companies listed on the TSX Venture Exchange, in each ... clean technology & life sciences, diversified industries and ... given to return on investment, market cap growth, trading volume ...
(Date:2/8/2016)... 2016  CytRx Corporation (NASDAQ: CYTR ), ... oncology, today announced that it has entered into ... Technology Growth Capital, Inc. and Hercules Technology III, ... --> --> ... financing under the loan and security agreement.  The ...
(Date:2/8/2016)... -- Novan, Inc. today announced that Director Robert A. Ingram ... Novan. In addition, Robert Keegan has been appointed to ... . --> North Carolina . ... total of $32.8 million of net proceeds in a private Mezzanine ... throughout the Research Triangle area of North Carolina ...
Breaking Biology Technology: