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Molecular Mimicry

Study suggests how 'flesh-eating' bacteria burrows through skin

WEDNESDAY, Dec. 5, 2001 (HealthDayNews) -- Streptococcus pyogenes, the bug that causes strep throat and the so-called "flesh-eating" disease, appears to be a wolf in sheep's clothing.

New research finds the organism is adept at burrowing through the skin thanks to a molecular equivalent of a friendly disguise -- an outer coat of bound-together sugars lined with a signaling compound called hyaluronic acid.

Normally, the compound tells neighboring skin cells to let go of each other. By exploiting this signal, the germ, also known as group A Streptococcus (GAS), can tunnel into normally impenetrable tissues and cause infection.

GAS is a bacterium commonly found on the skin and in the throat. It spreads through direct contact with infected mucus or sores. Most people carry the bacterium without any symptoms.

But it also can cause illnesses ranging in severity from strep throat and impetigo to necrotizing fasciitis, commonly called the "flesh-eating" disease, and streptococcal toxic shock syndrome (STSS). Several million cases of strep throat or impetigo occur annually in the United States. Of the roughly 600 Americans who develop necrotizing fasciitis, 20 percent will die, while more than half of the 300 patients who develop STSS will die.

Senior investigator Dr. Michael R. Wessels, an expert on infectious diseases at Children's Hospital in Boston, says many other types of bacteria have a polysaccharide outer coating like this type of strep, but GAS seems to be the only one with the hyaluronic acid component.

Wessels suspects that the hyaluronic acid-coated organisms latch onto a protein called CD44 that is found on the surface of human cells. CD44 is thought to be involved in cell growth and specialization and wound healing.

Wessels and colleague Colette Cywes found that GAS could move through roughly three layers of human skin cells in culture, as well as through a thicker, cultured tissue sample containing multiple types of human skin cells. However, a strain of GAS that lacks the hyaluronic-acid outer coat barely could penetrate the samples.

When hyaluronic acid attaches to the CD44 receptors, it tells the cells to move, allowing the bacteria to burrow through the skin. When GAS binds to CD44 on skin and throat surface cells, it triggers the formation of "membrane ruffles" on the cells' surfaces and opens the attachments between cells, says Wessels.

"The latter phenomenon might be important in the ability of the bacteria to then penetrate into the host tissues," says Wessels.

"Hyaluronic acid is a polysaccharide that is a constituent of connective tissues of higher animals, including humans," says Wessels. "As a consequence of that, our immune system doesn't detect [it] as a foreign antigen." Surrounded by hyaluronic acid, GAS doesn't trigger a protective immune response.

Dr. Dennis L. Stevens, chief of the infectious diseases section at the Boise Department of Veterans Affairs Medical Center, in Boise, Idaho, says the findings describe a very important interaction between human host cells and GAS. "It usurps the body's ability to detect and make antibodies against it," says Stevens.

He predicts that other discoveries will follow. "It's a very, very complicated organism. It's going to take a while to understand all the ways that GAS interacts with the host immune system," says Stevens.

By understanding how GAS mimics this natural signaling pathway, Wessels says the findings show how the organism infects a host. "We might be able to exploit understanding this specific interaction with strategies for prevention or treatment. It should be possible to interfere with this interaction between the [hyaluronic acid outer coat] and CD44 with an agent that specifically blocks the CD44 receptors," he says.

In fact, Wessels says he's already shown in laboratory and animal studies that pre-treating the cells or the animals with hyaluronic acid can protect them from nasal sprays of GAS in the upper airway by already blocking receptors so the strep couldn't get through. "It's possible that an approach like that might actually have a clinical application," he says, but adds that such a therapy could be up to five years away.

What To Do

Your best defense against a GAS infection is regular, thorough hand washing, especially after coughing or sneezing and before you eat. If you develop a sore throat with a fever, see your health-care provider for a throat swab, and keep all wounds clean.

For more information on GAS, check the Centers for Disease Control and Prevention the National Institute of Allergy and Infectious Diseases or the Association of State and Territorial Directors of Health Promotion and Public Health Education.

SOURCES: Interviews with Michael R. Wessels, M.D., chief, division of infectious diseases, Children's Hospital, Harvard Medical School, investigator, Channing Laboratory, Boston; Dennis L. Stevens, M.D., Ph.D., chief, infectious diseases section, Boise Department of Veterans Affairs Medical Center, Boise, Idaho; Dec. 6, 2001, Nature
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