Group A Streptococcus (group A strep) is the ‘Jack of All Trades’ of pathogens. The adaptable microbes can colonize the throat, skin, genitals, and more. They infect hundreds of millions of people every year and kill more than 500,000.
Most infections don’t advance beyond an aggravating sore throat or rash. However, from time to time, they do end up threatening lives with conditions such as toxic shock syndrome, rheumatic fever, or flesh-eating disease.
There are antibiotics available that fight group A strep, although resistance to some of these drugs is growing among strains worldwide. Furthermore, there are no vaccines commercially available to avoid infection. If researchers could find new treatments to combat these pathogens, it could prevent hundreds of thousands of deaths annually around the world.
And so, a team of California scientists has been studying group A strep’s stealthy strategy for several years now. They hope to develop a new treatment for infections. By “stealthy strategy,” they are referring to the way the pathogen’s cells act as masters of disguise to hide from the immune systems killer cells.
David Gonzalez, a microbiologist and biochemist at the University of California, San Diego, explained:
Various types of harmful bacteria, for example, masquerade as human cells to evade the immune system, blanketing their surfaces with molecules that resemble our own. The clever trick effectively gives the pathogens cloaks of invisibility.
The research reveals how the bacteria that cause strep throat can avoid being snuffed out by the immune system – and it’s a whole new form of eerie microbial mimicry at play. The bacteria (group A strep) rip apart red blood cells to then dress themselves up in the shreds. The bacteria wreak havoc as they circulate the body concealed, decked out in the smart disguise. The researchers proved this to be so with mouse experiments.
The researchers also discovered that there is a specific protein in the bacteria responsible for the dress-up action, and when they snip it out of the strep genome, the microbes are left exposed. Without that protein there to dress up the bacteria in its cloak of invisibility, the immune system was able to attack the pathogens and prevent a potentially deadly infection. The study has been published in the journal Cell Reports.
Martina Sanderson-Smith, A University of Wollongong molecular microbiologist who was not involved with the study, said:
Understanding the biology behind group A strep’s bloody disappearing act might aid the search for new drugs that uncloak the bacteria so they can be effectively cleared or killed. This is an example of discovery science at its best.
To better understand the bacteria’s elusive ways, the team studied the collection of molecules produced by the pathogen during infection. That’s how they discovered that some of the molecules, including some proteins, stick to red blood cells and rip them apart. Knowing this, the researchers employed nanoparticles coated with particles of blood cells as bait. Their nanoparticles successfully snared a new protein they hadn’t known about called the S protein.
The S protein is the molecule responsible for dressing up the bacteria. It’s “sticky,” and that’s how it works. The fragments of broken up blood cells get stuck to the S protein. This clever maneuver allows the bacteria to pass as the very cells they’d destroyed.
Co-first author Anaamika Campeau, a biochemist in Gonzalez’s lab, said:
The deception is an unusual tactic, but an effective one. To hide any features that might incriminate group A strep as foreign invaders, the microbes plaster themselves with pieces of cells the immune system sees all the time and knows not to attack. Once we kind of came to that idea, it all sort of fell into place.
When the researchers plopped group A strep cells into solutions of human blood along with red blood cells, the bacteria turned bright crimson. The bloody disguise worked so well that the immune cells were completely confused and mostly failed to capture and kill the invaders.
Next, the team generated a mutant strain of the bacteria that didn’t possess the S protein. When they plopped that into the solution of human blood along with red blood cells, the bacteria struggled to disguise itself and only turned faintly pink in the presence of blood. The immune cells were not tricked this time around, and they quickly devoured the invaders.
The researchers wanted to test the potency of S protein’s evasive effects, so they injected mice with either one of the two bacterial strains (the original or the mutant). Of the mice infected with typical group A strep, nearly all of them lost weight and died. On the other hand, of the mice infected with the team’s mutant microbes, all of them survived and kept a healthy weight.
Tiara Pérez Morales, a molecular microbiologist at Benedictine University who wasn’t involved in the study, said:
Microbes mimicking host cells isn’t a new biological trick. But the new study puts a plot twist on an old story. They’re putting on a costume and pretending they’re red blood cells. I don’t think I can think of anything else like it.
To test their findings one more way, the researchers conducted a final experiment. They dosed the mice with either a saline solution or the mutant bacteria. Three weeks later, they reinfected them all with typical group A strep. Of the animals given a saline solution, 90% of them died within ten days. On the other hand, of the animals given the mutant strain, seven out of eight (around 87.5%) survived.
Pérez Morales said:
That was exciting to see. The findings could prove especially significant if they can be repeated in other members of the Streptococcus genus, which includes several other pathogens that appear to also make S protein.
The loss of the S protein severely disabled the bacteria. Sanderson-Smith said this discovery has led to an appealing new approach for drugs in the future. It may even develop beyond simply a means to unmask group A strep. Gonzales believes that S-protein-based treatments could also become like a living vaccine. He said that they gave mice a hefty dose of the mutant bacteria, and the animals began to churn out immune proteins, which is a sign that the altered strain had alerted the body to its presence without causing any serious harm.
The issue of antibiotic resistance only continues to inflate worldwide, and this study is a perfect example of taking on a creative new approach to treatment.
Pérez Morales said:
We need alternatives. We can’t just keep hitting this problem with antibiotics.
For now, lots more research is needed before human vaccination with this mutant strain can even be considered. Pérez Morales and Sanderson-Smith caution that microbes and the immune cells they circumvent are ever-evolving and extremely complex, and what works in mice doesn’t always translate into humans.
