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!
NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases
Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
21.03.2018 | Physics and Astronomy
21.03.2018 | Materials Sciences
21.03.2018 | Life Sciences