Panton-Valentine leukocidin (PVL) is one of many toxins associated with S. aureus infection. Because it can be found in virtually all CA-MRSA strains that cause soft-tissue infections, several research groups previously have proposed that PVL is the key virulence factor.
But new evidence strongly suggests that is not the case. A study led by NIAID researchers at Rocky Mountain Laboratories (RML) in Hamilton, MT, shows that the two major epidemic CA-MRSA strains and the same strains with PVL removed are equally effective at destroying human white blood cells--our primary defense against bacterial infections--and spreading disease. The findings, which appear online in The Journal of Infectious Diseases, are surprising because many scientists had presumed that CA-MRSA uses PVL to target and kill specific white blood cells known as neutrophils.
"The Staphylococcus aureus bacterium is a growing global public health menace because of its rapid spread from hospital settings into communities of healthy people," says NIAID Director Anthony S. Fauci, M.D. "This is an evolving pathogen that in recent decades has developed resistance to common medical treatments and now is finding new mechanisms to spread and cause severe illness."
About 75 percent of CA-MRSA infections are localized to skin and soft tissue and usually can be treated effectively. CA-MRSA strains have enhanced virulence, meaning they can infect otherwise healthy people. One of the biggest problems with CA-MRSA skin infections is that they spread rapidly and have the potential to cause illness much more severe than traditional hospital-associated MRSA infections, where PVL is less common. These life-threatening infections can affect vital organs and lead to widespread infection (sepsis), toxic shock syndrome and flesh-eating pneumonia. It is not known why some healthy people develop CA-MRSA skin infections that are treatable whereas others infected with the same strain develop severe infections or die.
Scientists had recognized a connection between MRSA strains that contain PVL and the increased occurrence and severity of CA-MRSA disease, though no one had directly tested the role of PVL in CA-MRSA virulence. In striving to learn more about CA-MRSA, the RML scientists, with their colleagues at the International Center for Public Health (ICPH) in Newark, NJ, and the Université Claude Bernard in Lyon, France, decided to test the PVL virulence theory, thinking that if they could understand the role of this toxin in disease, they could more quickly diagnose serious cases and develop effective treatments.
In addition to observing the destruction of human white blood cells regardless of whether PVL was present, the researchers also used mouse models to learn that CA-MRSA strains are just as pathogenic with or without PVL present. These findings were seen in tests with mice that displayed skin and soft-tissue infection and bacterial sepsis.
"The strains were just as deadly with or without the PVL toxin," says lead investigator Frank DeLeo, Ph.D., of RML. "Unexpectedly, the average abscess volume in mice infected with strains absent the PVL was slightly greater than those containing the toxin. The strong association between PVL and CA-MRSA makes the toxin an excellent marker to track community strains, but the assumption that it is the major virulence determinant driving this epidemic is simply not true."
These findings are significant because some infectious disease physicians who treat MRSA patients had begun questioning whether PVL truly led to severe illness, says Barry Kreiswirth, Ph.D., study co-author and a leading staphylococcal epidemiologist from ICPH in Newark. He adds, "We routinely receive calls from clinical microbiology laboratories asking to test for the presence of PVL, and it is hard to dissuade them that the PVL results will not affect patient care. Hopefully, the robust and contrary findings in our study provide the experimental evidence to convince the staphylococcal researchers and clinicians that PVL is not a significant virulence factor."
Next, Dr. DeLeo says his group will shift away from PVL and try to determine exactly which toxin or other mechanism in S. aureus kills white blood cells and allows the spread of CA-MRSA infection.
Ken Pekoc | EurekAlert!
WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf
First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology