Peptides found in the protein cytokeratin 6A in humans protect from microbial infection by inhibiting bacterial mobility.

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Keratin is a protein that is renown for its help in managing the structural integrity of a cell; what was not previously known about keratin, however, is that it is also a plentiful source of peptides that have antimicrobial properties. Researchers began investigating keratin's properties after pondering on the resilience of the human eye. How is it that this exposed surface is rarely the site of infection? What defense mechanisms has the cornea developed to protect itself against the ever-hungry microbial world? It is believed that the glycine-rich portions of the peptides in keratin immobilize bacterial cells through their permeability of the bacterial membrane. This discovery could provide insight into new, chemical-free antiseptics and cleaners.

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"Keratins have long been recognized as indispensable structural materials that maintain cell integrity and resilience. Here we show a role for human keratins in epithelial innate immunity as a source of endogenous antimicrobial peptides. Specifically, the data show that short peptide fragments derived from the C terminus of hK6A are found within differentiated human corneal epithelial cells, that these peptides exert antimicrobial activity against multiple bacterial pathogens in vitro, and that depletion of K6A in vivo reduces corneal defense against bacterial attachment. Antimicrobial activity of these coiled, glycine-rich peptides (termed KDAMPs) is not constrained by stringent secondary structure or net charge requirements. Direct visualization showed that KDAMPs bind to P. [Pseudomonasaeruginosa, that they induce cell wall/membrane permeabilization, and that they inhibit bacterial motility. Together, we believe these data establish a new role for cytokeratin 6 in protecting mammalian epithelia from bacterial infection." (Tam et al. 2012:3676)

"Keratins are an ancient and extremely diverse set of proteins (44). In humans, keratins comprise a large family (54 functional genes) distributed intracellularly and extracellularly among multiple tissues, including skin, teeth, hair, nails, and mucosal surfaces (45, 46). Within epithelial cells, basic (type II) and acidic (type I) cytokeratins work as complementary pairs to form heteropolymeric intermediate filaments of the cytoskeleton and are key structural components of human cells and tissues. Cytokeratins also play roles in wound healing and tissue regeneration (47) in intracellular signaling and apoptosis (46). Discovery of antimicrobial and cytoprotective properties for K6A-derived peptides could advance our understanding of the functional significance of cytokeratin 6, and other keratins, in general. For example, it might explain the universal presence of keratins in cells and tissues of virtually all species and their diversity within species." (Tam et al. 2012:3676)

Journal article
Cytokeratins mediate epithelial innate defense through their antimicrobial propertiesJournal of Clinical InvestigationSeptember 24, 2012
Connie Tam, James J. Mun, David J. Evans, Suzanne M.J. Fleiszig

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