A new channel-forming antibiotic from Streptomyces coelicolor A3(2) which requires calcium for its activity.

A recently discovered antibiotic (CDA; calcium-dependent antibiotic) of Streptomyces coelicolor A3(2) was found to be effective against a wide range of Gram-positive bacteria only in the presence of calcium ions. Producer and non-producer strains were identified and several media tested for their ability to support antibiotic production. The action of calcium was not simulated by any of the other cations tested. The antibiotic was found to induce discrete conductance fluctuations in planar lipid bilayer consistent with a channel-forming action. The electrical potential difference caused by a concentration difference of various salts across the CDA-containing bilayer, showed the channel to be cation-selective but of a size that discriminated against tetramethyl ammonium and choline ions. The data indicate that the antibiotic activity of CDA is due to its action as a calcium-dependent ionophore.

[1]  B. Rudd,et al.  Genetics of actinorhodin biosynthesis by Streptomyces coelicolor A3(2). , 1979, Journal of general microbiology.

[2]  A. Finkelstein,et al.  Aqueous pores created in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B. , 1973, Membranes.

[3]  D. E. Goldman POTENTIAL, IMPEDANCE, AND RECTIFICATION IN MEMBRANES , 1943, The Journal of general physiology.

[4]  J. Beringer R factor transfer in Rhizobium leguminosarum. , 1974, Journal of general microbiology.

[5]  D. Hopwood Genetic analysis and genome structure in Streptomyces coelicolor , 1967, Bacteriological reviews.

[6]  H. Lardy,et al.  A23187: a divalent cation ionophore. , 1972, The Journal of biological chemistry.

[7]  E. Bamberg,et al.  Temperature-dependent properties of gramicidin A channels. , 1974, Biochimica et biophysica acta.

[8]  D. Hopwood LINKAGE AND THE MECHANISM OF RECOMBINATION IN STREPTOMYCES COELICOLOR * , 1959, Annals of the New York Academy of Sciences.

[9]  S. Waksman,et al.  STREPTOMYCES COELICOLOR MÜLLER AND STREPTOMYCES VIOLACEORUBER WAKSMAN AND CURTIS, TWO DISTINCTLY DIFFERENT ORGANISMS , 1959, Journal of bacteriology.

[10]  H. Ti Tien,et al.  METHODS FOR THE FORMATION OF SINGLE BIMOLECULAR LIPID MEMBRANES IN AQUEOUS SOLUTION , 1963 .

[11]  A. Hodgkin,et al.  The effect of sodium ions on the electrical activity of the giant axon of the squid , 1949, The Journal of physiology.

[12]  T. Hendriks,et al.  Movement of calcium through artificial lipid membranes and the effects of ionophores. , 1975, Biochimica et biophysica acta.

[13]  D. Hopwood,et al.  Identification of the antibiotic determined by the SCP1 plasmid of Streptomyces coelicolor A3(2). , 1976, Journal of general microbiology.

[14]  E. Bamberg,et al.  Single channel conductance at lipid bilayer membranes in presence of monazomycin. , 1976, Biochimica et biophysica acta.

[15]  L. Ermishkin,et al.  Properties of amphotericin B channels in a lipid bilayer. , 1977, Biochimica et biophysica acta.

[16]  J. Bangham,et al.  The interaction of detergents with bilayer lipid membranes. , 1978, Biochimica et biophysica acta.

[17]  S. Hladky,et al.  Molecular Mechanisms of ION Transport in Lipid Membranes , 1974 .

[18]  M. Okanishi,et al.  Formation and reversion of Streptomycete protoplasts: cultural condition and morphological study. , 1974, Journal of general microbiology.

[19]  A. Finkelstein,et al.  Permeability and electrical properties of thin lipid membranes. , 1968, The Journal of general physiology.

[20]  J. Sandblom,et al.  Membrane potentials at zero current. The significance of a constant ionic permeability ratio. , 1967, Biophysical journal.

[21]  G. Sermonti,et al.  Genetic Recombination in Streptomyces , 1955, Nature.

[22]  L. Stryer,et al.  Simultaneous fluorescence and conductance studies of planar bilayer membranes containing a highly active and fluorescent analog of gramicidin A. , 1975, Journal of molecular biology.

[23]  J. Collins,et al.  THE EFFECT OF THE PLANT HORMONE ABSCISIC ACID ON LIPID BILAYER MEMBRANES , 1979 .

[24]  R. Kirby,et al.  Plasmid-determined antibiotic synthesis and resistance in Streptomyces coelicolor , 1975, Nature.

[25]  D. Hopwood,et al.  CDA is a new chromosomally-determined antibiotic from Streptomyces coelicolor A3(2). , 1983, Journal of general microbiology.

[26]  A. Finkelstein,et al.  The Ion Permeability Induced in Thin Lipid Membranes by the Polyene Antibiotics Nystatin and Amphotericin B , 1970, The Journal of general physiology.

[27]  B. Rudd,et al.  A pigmented mycelial antibiotic in Streptomyces coelicolor: control by a chromosomal gene cluster. , 1980, Journal of general microbiology.

[28]  S. Hladky,et al.  Ion transfer across lipid membranes in the presence of gramicidin A. I. Studies of the unit conductance channel. , 1972, Biochimica et biophysica acta.