Sialic Acid-expressing Pathogens
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Sialic acids are major cell surface sugars involved in many biological functions in the Deuterostome lineage of animals (Vertebrates and so-called "higher" invertebrates. In contrast they are rarely found in other branches of life. A striking exception is the expression of sialic acids on certain pathogens, which use convergent evolutionary mechanisms to display sialic acids in vertebrate-like patterns, thereby eluding the immune system is a variety of ways. Remarkably, the majority of such sialic-acid expressing pathogens known to date are either human-specific or human-specialized. For various reasons, ascertainment basis seems an unlikely explanation Interestingly, pathogens cannot reinvent the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) , but can do so with the human-enriched sialic acid N-acetylneuraminic acid (Neu5Ac). One possible explanation is that these organisms are thus "taking advantage" of this human-specific change in sialic acid evolution, by displaying the human Neu5Ac sialic acid and "hijacking" the intrinsic inhibitory functions of certain human innate immune cell Siglecs that have undergone evolutionary changes to recognize Neu5Ac, since the human-specific loss of Neu5Gc, about 2-3 million years ago. Of note, many of these pathogens lethally infect human fetuses, neonates and infants, often involving the brain, and were thus likely selective forces in human evolution. Interestingly, Siglec-11 expression in microglia is also a uniquely human condition. Perhaps brain-invading sialic acid pathogens iteract with this Siglec? Overall, it is reasonable to suggest that sialic acid pathogens have evolved to take advantage of the unusual sialic acid biology of humans.
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