L. Beven et al., Correlation between anti-bacterial activity and pore sizes of two classes of voltage-dependent channel-forming peptides, BBA-BIOMEMB, 1421(1), 1999, pp. 53-63
Anti-bacterial activities were compared for two series of voltage-dependent
pore-formers: (i) alamethicin (Alm) and its synthetic analogs (Alm-dUL) wh
ere alpha-amino-isobutyric acid residues (Aibs) were replaced by leucines a
nd selected key residues substituted and (ii) homologous voltage sensors of
the electric eel sodium channel (repeats S4L45 (III) and S4L45 (IV)). Spir
oplasma melliferum, a bacterium related to the mycoplasmas, was used as a t
arget cell. The data show that with respect to growth inhibition, cell defo
rmation and plasma membrane depolarization, the highest efficient peptide r
emained natural Aim although the minimal inhibitory concentrations of its L
eu analogs were within the same range as the parent molecule, except for Al
m-dUL P14A. Thus, as for the pore-forming activity observed in artificial m
embranes and for the toxicity towards mammalian cells, proline-14 proved to
be a critical residue for the anti-bacterial activity of alamethicin. Rega
rding the sodium voltage sensors, their anti-bacterial efficiency was at le
ast 10 times lower although they promoted spiroplasma cell agglutination. T
he anti-bacterial activities of the peptides were correlated with their por
e-forming properties, especially with the apparent and mean number of monom
ers per conducting aggregate ([N]) when both peptide families were consider
ed and, secondly, with mean open times (tau(o)) within each family. This su
ggests that although they may form 'raft-like' structures, the mechanism un
derlying anti-bacterial activity of Aim and its active analogs, as well as
the S4L45 voltage sensors with the S. melliferum plasma membrane, is predom
inantly through pore-formation according to the 'barrel-stave' mechanism. (
C) 1999 Elsevier Science B.V. All rights reserved.