Study Describes How Protein 'Camouflages' Strep A


A previously uncharacterized protein called S protein helps Group A Streptococcus bind to the membrane of red blood cells in order to hide from the patient’s immune system.

New research offers a novel explanation for the virulence of Group A Streptococcus and suggest a possible new avenue by which to attack the potentially deadly bacteria.

Investigators at the University of California, San Diego, and Emory University say they have been able to describe the function of a protein, dubbed “S protein,” which appears to help Group A Streptococcus (GAS) “hide” from the host’s immune cells. The findings were published this month in Cell Reports.

According to the study, GAS produces S protein, which in turn binds to the membrane of red blood cells, thereby shielding GAS from the host’s immune response and increasing virulence.

David J. Gonzalez, an assistant professor in the Department of Pharmacology at UCSD’s Skaggs School of Pharmacy and Pharmaceutical Sciences, said the research is important because GAS remains a very significant public health threat. He noted that more than 700 million people worldwide are diagnosed with GAS-related illnesses each year. And while the most common treatment for GAS (penicillin) remains widely available and effective, it doesn’t work all of the time. In fact, Gonzalez and colleagues note that in some parts of the world penicillin has a treatment failure rate of up to 40%. He noted that the main alternative to penicillin also has significant problems.

“Some individuals are allergic to penicillin and as an alternative approach are administered erythromycin,” he told Contagion®. “Erythromycin-resistant GAS strains have emerged in recent years in mainland China and the [US Centers for Disease Control and Prevention] has pinpointed erm-resistant strains as a 'serious' concern in their report on antibiotic resistant in the US.”

Gonzalez also noted that at present there’s no vaccine against GAS.

To better understand the virulence of GAS, Gonzalez and colleagues used biomimetic virulomics, a relatively recent nanotechnological tool to analyze proteins secreted by GAS. Their observations of S protein led to the hypothesis that the protein essentially uses red blood cell membranes as camouflage. They then compared the survival of GAS to that of a mutant bacterial strain that did not include S protein. Using a mouse model, they found that survival of the mice varied greatly depending on the presence of S protein. With the protein, mouse mortality was 90%; without it, mortality fell to just 40%. Virulence also decreased when S protein was taken away.

The findings suggest that investigators might be able to increase survival and reduce virulence in patients with GAS infection if they can find a way to inactivate S protein.

Gonzalez said there’s still a long way to go before that can be done. However, he said this was an important first step.

“We still need to perform more work to better understand the mechanism of red blood cell binding facilitated by S protein in order to target this novel mechanism of parthenogenesis for therapeutic development,” he said.

While it’s still unknown if the findings can be used to create a human therapeutic, he said the results in the mouse model were compelling.

“One thing that can be said for certain is: S protein is a bona fide virulence factor absolutely required for GAS to cause an invasive infection in a mouse model and that the GAS strain null of S protein can be used as a live attenuated vaccine in mice,” he said.

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