Mechanisms of antibacterial action of tachyplesins and polyphemusins, a group of antimicrobial peptides isolated from horseshoe crab hemocytes.

Tachyplesins I and II and polyphemusins I and II, cationic peptides isolated from the hemocytes of horseshoe crabs, show bactericidal activities with similar efficiencies for both gram-negative and gram-positive bacteria. Tachyplesin I inhibited bacterial growth irreversibly within 40 min. A subinhibitory concentration of tachyplesin I sensitized gram-negative bacteria to the bactericidal actions of novobiocin and nalidixic acid, although polymyxin B-resistant strains which have altered lipopolysaccharides were susceptible to tachyplesin I. This implies that tachyplesin permeabilizes the outer membrane and that the likely target of its action is outer membrane constituents other than lipopolysaccharides. On the other hand, a defensin-susceptible phoP strain of Salmonella typhimurium was also susceptible to tachyplesin I. Tachyplesin I rapidly depolarized the inverted inner-membrane vesicles of Escherichia coli. These results suggest that depolarization of the cytoplasmic membrane, preceded by the permeabilization of the outer membrane for gram-negative bacteria, is associated with tachyplesin-mediated bactericidal activity. The similarity between the actions of tachyplesin and those of defensin was discussed.