Group B Streptococcus and Platelets: A Wolf in Sheep's Clothing

March 25, 2019

— Heather Buschman, PhD

Since newborn babies haven’t encountered many pathogens, they haven’t yet built up a fully robust immune response. But they do have what’s known as “innate immunity” — a collection of bacteria-busting molecules and cells we’re all born with, such as neutrophils and macrophages.

More recently, scientists have come to appreciate another member of the innate immune system: platelets. Better known for their role in clotting blood, it turns out platelets also help keep the bloodstream clear of bacteria. For example, platelets can directly kill Staphylococcus aureus (staph bacteria), a common but sometimes life-threatening microbe.

But, oddly enough, platelets are not a threat to group B Streptococcus (GBS), the leading cause of invasive bacterial infections in newborns, which can lead to pneumonia, sepsis and meningitis. In a study published March 25, 2019 by the Proceedings of the National Academy of Sciences, UC San Diego researchers discovered that GBS are not only resistant to killing by platelets, these bacteria grow better in their presence.

Here we break down the study with the help of Victor Nizet, MD, professor of pediatrics and pharmacy at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, and Satoshi Uchiyama, MD, PhD, assistant project scientist in Nizet’s lab. They led the study along with Jamey Marth, PhD, at UC Santa Barbara and Sanford Burnham Prebys Medical Discovery Institute.

How do GBS manage to evade platelets?

Group B Streptococcus (purple) and platelets (orange) as viewed by electron microscopy.

We know that GBS have a somewhat unusual capsule — each bacterium is coated with sialic acid, a sugar molecular that’s also found on the surface of all human cells. We’ve found in previous studies that the sialic acid capsule helps GBS fend off other components of the immune system. In this study, we found that the sialic acid capsule helps GBS avoid platelets in two ways: 1) the capsule blocks antimicrobial peptides produced by platelets, and 2) it engages an “off switch,” an inhibitory receptor (siglec), on the platelet surface that prevents the cell’s activation.

Why is this exciting?

Until now, it was a bit of a mystery how GBS could spread through an infant’s body so easily, causing such severe disease along the way, without getting killed in the bloodstream as we might expect. This study revealed completely new aspects of both GBS and platelets. In fact, this is likely the first time anyone has discovered a mechanism bacteria have evolved to specifically protect themselves from platelets.

This is also a great example of “molecular mimicry,” in which by decorating its surface with the human-like sugar sialic acid, the bacterium is able survive and proliferate in the bloodstream. In that way, GBS is like a wolf in sheep’s clothing … the bacteria are fooling platelets into thinking they are human cells. Even more troubling in this case, the capsule is acting both as a disguise and a shield.

What’s next?

The more we know about how platelets play a role in the innate immune response and the many tricks GBS uses to survive, the better we are equipped to prevent or treat this often deadly infection. Next we want to explore how we might interfere with bacterial escape mechanisms or boost platelet immune functions, better enabling them to fight infections.

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