RL-37, an alpha-helical antimicrobial peptide of the rhesus monkey.

Rhesus monkey bone marrow expresses a cathelicidin whose C-terminal domain comprises a 37-residue alpha-helical peptide (RL-37) that resembles human LL-37. Like its human counterpart, RL-37 rapidly permeabilized the membranes of Escherichia coli ML-35p and lysed liposomes that simulated bacterial membranes. When tested in media whose NaCl concentrations approximated those of extracellular fluids, RL-37 was considerably more active than LL-37 against staphylococci. Whereas human LL-37 contains five acidic residues and has a net charge of +6, rhesus RL-37 has only two acidic residues and a net charge of +8. Speculating that the multiple acidic residues of human LL-37 reduced its efficacy against staphylococci, we made a peptide (LL-37 pentamide) in which each aspartic acid of LL-37 was replaced by an asparagine and each glutamic acid was replaced by a glutamine. LL-37 pentamide's antistaphylococcal activity was substantially greater than that of LL-37. Thus, although the precursor of LL-37 is induced in human skin keratinocytes by injury or inflammation, its insufficiently cationic antimicrobial domain may contribute to the success of staphylococci in colonizing and infecting human skin.

Dicynthaurin: an antimicrobial peptide from hemocytes of the solitary tunicate, Halocynthia aurantium.

We isolated a novel antimicrobial peptide, dicynthaurin, from hemocytes of a tunicate, Halocynthia aurantium. The native peptide had a mass of approximately 6.2 kDa and was composed of two 30-residue monomers without sequence homology to any previously identified peptides (ILQKAVLDCLKAAGSSLSKAAITAIYNKIT). Most cynthaurin molecules were C-terminally amidated and were linked covalently by a single cystine disulfide bond. When performed in membrane-mimetic environments, circular dichroism studies of dicynthaurin revealed largely alpha-helical conformations. Dicynthaurin's broad-spectrum activity encompassed Gram-positive (Micrococcus luteus, Staphylococcus aureus, Listeria monocytogenes) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), but not Candida albicans, a fungus. Although dicynthaurin was purified from a marine invertebrate, its antimicrobial activity was optimal at NaCl concentrations below 100 mM. This suggests that the antimicrobial actions of this molecule may take place intracellularly (e.g., within a phagosome) rather than extracellularly.