‘A very wily opponent’: New findings bring scientists closer to defeating group A strep

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Under magnification, group A streptococci look almost cuddly, like tiny Timbits bundled in furry coats. But to the chagrin of researchers such as Dr. James Musser, these pesky and sometimes deadly pathogens have proven to be deceptively tough.

"I always describe group A strep as a very wily opponent. And it doesn't get less wily; it gets more wily as the years go on," says Musser, chair of the department of pathology and genomic medicine at the Texas health-care organization Houston Methodist.

For nearly 20 years, Musser has joined scientists around the world in search of ways to defeat group A streptococcus, the bacteria responsible for a continuing outbreak in London, Ont., that has claimed nine lives. Their quest has been a long and vexing one. It's estimated that group A strep causes more than 600 million cases of streptococcal pharyngitis, or strep throat, worldwide every year and, in rare cases, it can cause far more serious infections such as streptococcal toxic shock syndrome and necrotizing fasciitis, also known as flesh-eating disease.

In addition to London, cases of invasive group A strep have recently surfaced in other parts of the country, including around Vancouver, Toronto, Calgary and Montreal.

Infections are generally treated with antibiotics. But beyond containing the bacteria through run-of-the-mill preventive measures, such as frequent hand-washing, covering one's mouth and nose when coughing and sneezing, and avoiding the sharing of drugs and needles, the ability to protect ourselves against outbreaks remains elusive.

Through their efforts to develop a vaccine, however, researchers are gaining valuable insight into how group A streptococcus works and behaves. Their latest findings edge them ever closer to the goal of beating the bug.

As Musser explains, scientists have been working on a group A strep vaccine for at least 100 years, to no avail. One of the major hurdles is that unlike many other bacteria and viruses for which vaccines have successfully been developed, there is wide genetic variation in group A strep.

With more than 220 known strains of the bacteria, a vaccine developed to fend off one strain wouldn't necessarily protect people from other strains, says Dr. Partho Ghosh, a professor in the department of chemistry and biochemistry at University of California San Diego.

Moreover, group A strep produces different toxins and molecules depending on the type of infection and where in the body the bacteria are growing, Musser says. For instance, there's a whole menu of factors involved that allow the bacteria to cause strep throat, whereas if it gets into the bloodstream, it produces an entirely different set of toxins and molecules that allow it to cause necrotizing fasciitis, he says. This contributes to the challenges of homing in on a target for a vaccine.

Exactly how group A strep cause illnesses with such range in severity is still something of a puzzle. (Some people can carry the bacteria and experience no symptoms at all.) Musser says certain strains tend to behave more aggressively, causing significantly more cases of invasive infection such as necrotizing fasciitis, while others act like "pathogenic wimps" – they may cause throat infections, but lack the chutzpah to cause anything more serious.

Ghosh, meanwhile, suggests there are probably multiple factors that prompt a superficial, strep-throat-causing strain to undergo a genetic change to become an invasive one. He says there's a hypothesis within the field that may explain how group A strep works.

Consider things, for a moment, from the bacteria's perspective: "What group A strep is really trying to do is to get rid of its other bacterial competitors," Ghosh says.

To do this, it tickles the host's immune system, triggering an inflammatory response that will kill competing bacteria, he says. Since group A strep tends to be more resilient to inflammatory responses, it can survive this attack from the host. But, Ghosh says, if it overstimulates the immune system, provoking a massive response, the bacteria may then get access to deep tissues and become invasive.

"It's not really trying to cause an invasive disease," he says. After all, he says, from an evolutionary viewpoint, it's not in the bacteria's best interest to become invasive; death to the host also means a dead end for the bug.

Group A strep's furry coat, known as the M protein, allows it to evade the human immune system, Ghosh says. Because this outer protein coat is different for each strain, one of the proposed approaches some scientists have been working on has been to create a vaccine out of multiple M proteins, with the aim of protecting against several strains of the bacteria at a time, he says.

This approach so far seems promising, Ghosh says, but he and his colleagues believe they're on to something that could lead to a vaccine with a broadly neutralizing – or "type-promiscuous" rather than "type-specific" – response, akin to the promise of a universal flu vaccine that would protect against a wide variety of strains. Their solution relies on what can be thought of as a molecular skeleton key.

Several years ago, Ghosh explains, Swedish researchers discovered that in spite of their differences, M proteins of various group A strep strains are able to bind to the same human protein, called C4BP. This finding prompted Ghosh and his team to zero in on common sequence patterns hidden within all the different M proteins. Since it works with C4BP, he and his team suggest it may be possible to produce antibodies that can similarly bind to various M proteins.

Until that happens, though, public-health experts must try to control outbreaks as best as they can. That includes screening individuals within an outbreak cluster, treating those who have infections with antibiotics and applying basic measures such as hand hygiene and covering wounds, says Dr. Jonathan Gubbay, acting chief of microbiology at Public Health Ontario. In cases of invasive group A strep infection, antibiotics are also offered to those in close contact to infected individuals to reduce the chance of them getting sick as well.

And in the meantime, Musser continues to wrestle with his wily opponent.

"I hate to give you such a pessimistic outlook, but I think it's important for the lay public that we be honest," he says. "Commonly, the more we know, the less we know, because new pages are turned over, and things we thought 20 years ago were quite simple turn out to be not so at all. That's just always the way science is."