Group A Streptococcus bacteria — the cause of strep throat and flesh-eating infections — have been well studied for nearly a century. But researchers at University of California San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences recently made a surprising discovery: strep’s M protein alone wipes out macrophages, but not other types of immune cells. The macrophages’ self-sacrifice serves as an early warning of infection to the rest of the immune system.
The study, published August 7 in Nature Microbiology, revealed new roles for the well-studied M protein and for macrophages. The researchers said this new information should inform current strep vaccine strategies, many of which are based on M protein, and new treatment approaches for invasive infections and toxic shock syndrome, where hyper-immune responses can be detrimental.
M protein, an abundant, tentacle-like molecule that projects from the bacterium’s surface, is strep’s most important virulence factor. M protein is known to help the bacteria adhere to human tissues, make it harder for immune cells to engulf the bacteria, and bind or inhibit other components of the human immune system, such as antibodies and antimicrobial peptides.
“We thought we already knew pretty much everything there was to know about how M protein helps strep gain a foothold in the human body and avoid the immune system, so this was a totally unexpected discovery, and an especially dramatic thing for an immune cell to do,” said Victor Nizet, MD, professor of pediatrics and pharmacy, who led the study with Partho Ghosh, PhD, professor of chemistry and biochemistry at UC San Diego.
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