Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Effects on mollicutes (wall-less bacteria) of synthetic peptides comprising a signal peptide or a membrane fusion peptide, and a nuclear localization sequence (NLS) -- a comparison with melittin.
Biochim Biophys Acta. 1997 Oct 23;1329(2):357-69. Unique Identifier : AIDSLINE MED/98037478 Beven L; Chaloin L; Vidal P; Heitz F; Wroblewski H; Groupe Membranes et Osmoregulation, UPRES-A CNRS No. 6026,; Universite de Rennes 1, Campus de Beaulieu, France.
Abstract:
In order to investigate the effect of primary amphipathic peptides on mollicutes (wall-less bacteria), we have synthesised five molecules (P1, P2, P3, JM123, and JM133) comprising a 16 to 18-residue hydrophobic sequence and the nuclear localization sequence (NLS) PKKKRKV of simian virus 40 large-T antigen, C-terminated by a cysteamide group. The hydrophobic cluster was in P1 the signal sequence of the heavy chain of Caiman crocodilus immunoglobulin G and in JM123 the fusion peptide of human immunodeficiency virus 1 glycoprotein gp41 in which phenylalanine7 was replaced by a tryptophan residue. The homologues P2, P3, and JM133 were obtained by slight alterations of these sequences. Circular dichroism spectroscopy revealed that, in liposomes, P-series peptides were mainly under the form of beta-sheets whereas JM-series peptides displayed a high proportion of turns. These peptides proved to be bactericidal for some mollicutes, notably Acholeplasma laidlawii, but were much less potent than melittin. Furthermore, their antibiotic activity was independent of the average thickness of the plasma membrane hydrophobic core whilst that of melittin was inversely related to the thickness. Melittin and the synthetic peptides abolished spiroplasma cell motility and helicity, but only melittin and P-series peptides split the cells into globular forms displaying an average diameter of ca. 1 microm. In contrast to melittin, the synthetic peptides agglutinated spiroplasmas, suggesting that their polycationic NLS was exposed on the cell surface. P-series peptides decreased, though less efficiently than melittin, A. laidlawii and Spiroplasma melliferum membrane potential (delta psi) and transmembrane pH gradient (delta pH), at concentrations much lower than their minimal inhibitory concentrations whilst JM-series peptides had no effect on delta psi and delta pH in the same conditions. Actually, the bactericidal activity of these peptides towards mollicutes was proportional to their ability to collapse the electrochemical transmembrane potential.
Keywords: Alligators and Crocodiles Amino Acid Sequence Amino Acid Substitution Animal Anti-Infective Agents/*CHEMISTRY/PHARMACOLOGY Antigens, Viral, Tumor/CHEMISTRY Cell Wall/PHYSIOLOGY Circular Dichroism Comparative Study Human HIV Envelope Protein gp41/CHEMISTRY HIV-1 IgG/CHEMISTRY Immunoglobulins, Heavy-Chain/CHEMISTRY Liposomes Melitten/*CHEMISTRY/*PHARMACOLOGY Micelles Molecular Sequence Data Peptides/*CHEMISTRY/*PHARMACOLOGY Phenylalanine Phosphatidylglycerols Polyomavirus macacae Protein Conformation Sequence Alignment Spiroplasma/*DRUG EFFECTS/ULTRASTRUCTURE Structure-Activity Relationship Support, Non-U.S. Gov't Tryptophan JOURNAL ARTICLE 980228
M9820700
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
