Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Prickly protein

07.02.2014
Production of an exceptionally large surface protein prevents bacteria from forming clumps and reduces their ability to cause disease

A genetic mechanism that controls the production of a large spike-like protein on the surface of Staphylococcus aureus (staph) bacteria alters the ability of the bacteria to form clumps and to cause disease, according to a new University of Iowa study.


Images taken with a scanning electron microscope show wild-type bacteria (left) forming tight aggregates or clumps in the presence of blood proteins. In contrast, cells of the mutant strain (right) over produce a giant surface protein, have a spiky appearance, and do not clump tightly together. This clumping defect makes the mutant strain less deadly in an experimental model of the serious staph infection, endocarditis.

Credit: Alexander Horswill, University of Iowa

The new study is the first to link this genetic mechanism to the production of the giant surface protein and to clumping behavior in bacteria. It is also the first time that clumping behavior has been associated with endocarditis, a serious infection of heart valves that kills 20,000 Americans each year. The findings were published in the Dec. 2103 issue of the journal PLOS Pathogens.

Under normal conditions, staph bacteria interact with proteins in human blood to form aggregates, or clumps. This clumping behavior has been associated with pathogenesis -- the ability of bacteria to cause disease. However, the mechanisms that control clumping are not well understood.

In the process of investigating how staph bacteria regulate cell-to-cell interactions, researchers at the UI Carver College of Medicine discovered a mutant strain of staph that does not clump at all in the presence of blood proteins.

Further investigation revealed that the clumping defect is due to disruption of a genetic signaling mechanism used by bacteria to sense and respond to their environment. The study shows that when the mechanism is disrupted, the giant surface protein is overproduced -- giving the cells a spiny, or "porcupine-like" appearance -- and the bacteria lose their ability to form clumps.

Importantly, the researchers led by Alexander Horswill, PhD, associate professor of microbiology, found that this clumping defect also makes the bacteria less dangerous in an experimental model of the serious staph infection, endocarditis.

Specifically, the team showed that wild type bacteria cause much larger vegetations (aggregates of bacteria) on the heart valves and are more deadly than the mutant bacteria, which are unable to form clumps. The experimental model of the disease was a good parallel to the team's test tube experiments.

"The mutant bacteria that don't clump in test tube experiments, don't form vegetations on the heart valves," Horswill explains.

The team then created a version of the mutant bacteria that was also unable to make the giant surface protein. This strain regained the ability of form clumps and also partially regained its ability to cause disease, suggesting that the surface protein is at least partly responsible for both preventing clump formation and for reducing pathogenesis.

"Our study suggests that clumping could be a target for therapy," says Horswill. "If we could find drugs that block clumping, I think they would be potentially really useful for blocking staph infections."

Staph bacteria are the most significant cause of serious infectious disease in the United States, according to the Centers for Disease Control and Prevention (CDC). The bacteria are responsible for life-threatening conditions, including endocarditis, pneumonia, toxic shock, and sepsis. A better understanding of how staph bacteria causes disease may help improve treatment.

The team is now using screening methods to find small molecules that can block clumping. Such molecules will allow the researchers to investigate the clumping mechanism more thoroughly and may also point to therapies that might reduce the illness caused by staph infections.

The research was partially supported by grant funding from the National Institutes of Health (AI083211 and AI157153).

In addition to Horswill, the research team included Jeffrey Boyd, PhD, a former post doctoral researcher at the UI, whose early work initiated the study, and Patrick Schlievert, PhD, UI professor and chair of microbiology. UI scientists Jennifer Walker, Heidi Crosby, Adam Spaulding, Wilmara Salgado-Pabon, Cheryl Malone, and Carolyn Rosenthal were also part of the research team.

Jennifer Brown | EurekAlert!
Further information:
http://www.uiowa.edu

Further reports about: Prickly blood protein genetic mechanism heart valves test tube

More articles from Life Sciences:

nachricht New method opens crystal clear views of biomolecules
11.02.2016 | Deutsches Elektronen-Synchrotron DESY

nachricht Scientists from MIPT gain insights into 'forbidden' chemistry
11.02.2016 | Moscow Institute of Physics and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Production of an AIDS vaccine in algae

Today, plants and microorganisms are heavily used for the production of medicinal products. The production of biopharmaceuticals in plants, also referred to as “Molecular Pharming”, represents a continuously growing field of plant biotechnology. Preferred host organisms include yeast and crop plants, such as maize and potato – plants with high demands. With the help of a special algal strain, the research team of Prof. Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam strives to develop a more efficient and resource-saving system for the production of medicines and vaccines. They tested its practicality by synthesizing a component of a potential AIDS vaccine.

The use of plants and microorganisms to produce pharmaceuticals is nothing new. In 1982, bacteria were genetically modified to produce human insulin, a drug...

Im Focus: The most accurate optical single-ion clock worldwide

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...

Im Focus: Goodbye ground control: autonomous nanosatellites

The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.

Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...

Im Focus: Flow phenomena on solid surfaces: Physicists highlight key role played by boundary layer velocity

Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.

The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Im Focus: New study: How stable is the West Antarctic Ice Sheet?

Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels

A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Travel grants available: Meet the world’s most proficient mathematicians and computer scientists

09.02.2016 | Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

 
Latest News

New method opens crystal clear views of biomolecules

11.02.2016 | Life Sciences

Scientists take nanoparticle snapshots

11.02.2016 | Physics and Astronomy

NASA sees development of Tropical Storm 11P in Southwestern Pacific

11.02.2016 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>