Production of exceptionally large surface protein prevents bacteria from forming clumps

February 6, 2014
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

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.

The new study is the first to link this to the production of the giant 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 of the serious , 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 , don't form vegetations on the heart valves," Horswill explains.

The team then created a version of the that was also unable to make the giant surface protein. This strain regained the ability of form 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 are responsible for life-threatening conditions, including endocarditis, pneumonia, toxic shock, and sepsis. A better understanding of how 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.

Explore further: New vaccine protects against lethal pneumonia caused by staph bacteria

More information: PLOS Pathogens DOI: 10.1371/journal.ppat.1003819

Related Stories

New vaccine protects against lethal pneumonia caused by staph bacteria

December 20, 2013
University of Iowa researchers have developed a new vaccine that protects against lethal pneumonia caused by Staphylococcus aureus (staph) bacteria, including drug-resistant strains like MRSA.

Bacterial toxins cause deadly heart disease

August 20, 2013
University of Iowa researchers have discovered what causes the lethal effects of staphylococcal infective endocarditis - a serious bacterial infection of heart valves that kills approximately 20,000 Americans each year.

A quicker, cheaper way to detect staph in the body

February 2, 2014
Chances are you won't know you've got a staph infection until the test results come in, days after the symptoms first appear. But what if your physician could identify the infection much more quickly and without having to ...

Dental plaque bacteria may trigger blood clots

March 26, 2012
Oral bacteria that escape into the bloodstream are able to cause blood clots and trigger life-threatening endocarditis. Further research could lead to new drugs to tackle infective heart disease, say scientists presenting ...

Chronic exposure to staph bacteria may be risk factor for lupus, study finds

August 8, 2012
Chronic exposure to even small amounts of staph bacteria could be a risk factor for the chronic inflammatory disease lupus, Mayo Clinic research shows. Staph, short for Staphylococcus aureus, is a germ commonly found on the ...

Recommended for you

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.