Editors' ChoiceImmunology

Food as Antibiotic?

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Science Signaling  28 Jun 2011:
Vol. 4, Issue 179, pp. ec181
DOI: 10.1126/scisignal.4179ec181

Most fish eggs are fertilized and develop externally in the water, where they are exposed to pathogens in their aquatic environment. In addition to maternally contributed immune factors, yolk proteins have also been reported to have antimicrobial activity. Wang et al. confirmed that zebrafish embryo extracts contain phosvitin and that some of the antimicrobial activity (in colony-forming assays with various bacteria) was inhibited by an antibody against phosvitin. Injection of 8-cell-stage embryos with the antibody against phosvitin increased embryo mortality in response to infection with Aeromonas hydrophila (a zebrafish pathogen), and analysis of the rRNA of the pathogen in the embryos before death indicated that lysis of the pathogen was compromised in the antibody-injected embryos. Recombinant phosvitin purified from Escherichia coli exhibited antimicrobial activity and, unlike chicken phosvitin, which chelates iron, zebrafish phosvitin did not bind iron and did not require phosphorylation for antimicrobial activity. Analysis of the IC50 of zebrafish phosvitin for antimicrobial activity in vitro and analysis of the abundance of phosvitin in embryos at 12 and 24 hours after fertilization indicated that the 12-hour embryos had sufficient concentrations of phosvitin for effective antimicrobial action. Recombinant zebrafish labeled phosvitin bound to the surfaces of both Gram-negative and Gram-positive bacteria, and recombinant phosvitin bound to immobilized pathogen-associated molecular pattern molecules, lipopolysaccharide (LPS), lipoteichoic acid (LTA), and bacterial peptidoglycan (PGN), in a saturable and dose-dependent manner, suggesting that phosvitin is a pattern-recognition receptor. Deletion analysis and point mutation analysis revealed that the C-terminal 55 amino acids and residues Arg242, Ala201, and Ile203 were essential for antimicrobial activity in vitro, binding to LPS, LTA, and PGN, and protection from infection in embryos. Thus, yolk proteins serve not only as a food reserve but also as antimicrobial agents protecting developing embryos from infection.

S. Wang, Y. Wang, J. Ma, Y. Ding, S. Zhang, Phosvitin plays a critical role in the immunity of zebrafish embryos via acting as a pattern recognition receptor and an antimicrobial effector. J. Biol. Chem. 286, 22653–22664 (2011). [Abstract] [Full Text]

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