Antimicrobial molecules from Xenopus laevis and Squalus acanthias

Karen S Moore, University of Pennsylvania


Animals must defend themselves against pathogenic microorganisms and have evolved multiple mechanisms for this purpose. One defense mechanism is the synthesis of antimicrobial agents including low molecular weight molecules such as peptides, lipids, and alkaloids. An example of peptide defense is the magainin family, antimicrobial molecules stored in the skin of the frog Xenopus laevis (Zasloff, M. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5449-5453). This dissertation includes the characterization of the magainin family of peptides in the stomach of Xenopus. Nine antimicrobial peptides were purified and sequenced, one of which was a previously unreported peptide with the sequence GVLSNVIGYLKKLGTGALNAVLKQ. The peptide, designated PGQ (peptide with amino-terminal glycine and carboxy-terminal glutamine) is relatively basic, it has the potential to form an $\alpha$-helix, and its antimicrobial spectrum is similar to that of other members of the magainin family (Moore et al. (1991) J. Biol. Chem. 266, 19851-19857). The gastric mucosal cell which stores the magainin peptides is a multinucleated syncytial structure filled with dense granules, and is similar to the granular gland of the amphibian skin. It has been designated a granular multinucleated cell. Immunohisto-chemical and immunogold methods were used to demonstrate that magainin is stored in the granules present in these enteric cells (Moore et al. (1992) J. Histochem. Cytochem. 40, 367-378). As an extension of the research described above, extracts from the stomach tissue of the dogfish shark, Squalus acanthias were analyzed for the presence of antimicrobial activity. A novel antimicrobial aminosterol, named squalamine, was discovered. The structure of squalamine as determined by mass spectroscopy and nuclear magnetic resonance spectroscopy, is 3$\beta$-N-1- (N(3- (4-aminobutyl))-1,3 diaminopropane) -7$\alpha,24\zeta$-dihydroxy-$5\alpha$-cholestane 24-sulfate. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with spermidine. Squalamine exhibits potent antibacterial, antifugal, and antiprotozoan activity. It was demonstrated that the liver, gall bladder, spleen, testes, gills, and intestine of the shark also contain this antimicrobial aminosterol. The characterization of the peptide system in Xenopus stomach and the discovery of the novel aminosterol from the dogfish shark further our understanding of antimicrobial defense systems existing in animals.

Subject Area

Biochemistry|Microbiology|Molecular biology

Recommended Citation

Moore, Karen S, "Antimicrobial molecules from Xenopus laevis and Squalus acanthias" (1994). Dissertations available from ProQuest. AAI9427581.