The “Red Queen Effect” Writ Small
In what amounts to an evolutionary arms race at the molecular level, researchers at the University of California, San Diego School of Medicine describe how pathogens target or take advantage of key molecules on the surfaces of cells to evade detection or boost infection.
The findings are published in the March issue of The FASEB Journal.
All living cells are coated with chains of sugar molecules called glycans, with every organism sporting its own cloak of unique and characteristic glycan patterns, said first author Vered Padler-Karavani, PhD, a researcher at Tel Aviv University who originally worked with Ajit Varki, MD, co-director of UC San Diego’s Glycobiology Research and Training Center, and others on the study, including Takashi Angata, now at Academia Sinica in Taiwan.
In mammals, cell suface glycan chains are tipped with acidic sugars called sialic acids, which indicate to circulating immune system cells via receptors known as Siglecs that the cell is part of the host and not to be attacked as an invader.
However, certain pathogenic bacteria have evolved sialic acid containing glycans that mimic mammalian cells, using them to hide from and evade immune cells. Meanwhile, other pathogens, such as flu viruses, use sialic acids as binding targets to attack and infect host cells. In response to these dual pressures, mammalian sialic acids and Siglec receptors must be continuously tweaked to foil invasive microbes. But the faster evolving microbes adapt to the tweaks and the process repeats, over and over again.
The phenomenon is indicative of the so-called “Red Queen effect,” noted the researchers, a classic evolutionary concept inspired by Lewis Carroll’s novel Through the Looking-Glass. “Now, here, you see, it takes all the running you can do, to keep in the same place,” the queen says to Alice.
“Like Alice, who runs fast but finds herself still in the same spot, we find that certain sugar-receptors on our immune cells evolve rapidly in response to even more rapidly evolving pathogens, leading to a never-ending evolutionary arms race,” said Padler-Karavani.
The findings may have future implications for efforts to find new treatments and approaches to pathogens that try to take advantage of glycans, said Varki.