Amylosin from Bacillus amyloliquefaciens, a K+ and Na+ channel-forming toxic peptide containing a polyene structure

Toxicon. 2007 Jun 15;49(8):1158-71. doi: 10.1016/j.toxicon.2007.02.010. Epub 2007 Feb 25.

Abstract

Bacillus amyloliquefaciens strains isolated from the indoor environment of moisture-damaged buildings produce a 1197 Da toxin, named amylosin. Nuclear magnetic resonance (NMR) data showed that amylosin contains a chromophoric polyene structure and the amino acids leucine/isoleucine, proline, aspartic acid/asparagine, glutamic acid/glutamine and tyrosine. A quantitation method for amylosin was developed using commercially available amphotericin B as a reference compound and a known concentration of amylosin determined by NMR with the electronic reference to access in vivo concentration (ERETIC) method. Purified amylosin inhibited motility of boar sperm cells at an exposure concentration of 135 nM and hyperpolarized their cell membrane and depolarized their mitochondria at exposure to concentration of 33-67 nM for 10 min. In a 3-d exposure time only 27 nM of amylosin was needed to provoke the same toxicity functions. Amylosin was cytotoxic to feline lung cells at concentrations of <170 nM. Purified amylosin provoked adenosine 5'-triphosphate (ATP)-independent cation influx into isolated rat liver mitochondria (RLM), inducing swelling of the mitochondria at concentrations of 200 nM K(+) or >250 nM Na(+) medium. In the K(+)- or Na(+)-containing medium, amylosin uncoupled RLM, causing oxidation of pyridine nucleotides (PN), loss of the mitochondrial membrane potential, and suppressed ATP synthesis. Purified amylosin produced cation channels in black-lipid membranes (BLMs) with a selectivity K(+)>Na(+) at a concentration of 26 nM, i.e. the same concentration at which amylosin was toxic to boar sperm cells. The amylosin cation channels were cholesterol- and ATP-independent and more effective with K(+) than with Na(+). We propose that the toxicity of amylosin may be due its ionophoric properties, representing the first K(+)/Na(+) channel-forming substance reported from B. amyloliquefaciens.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acids / analysis
  • Animals
  • Bacillus / chemistry*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / isolation & purification
  • Bacterial Toxins / toxicity*
  • Cation Transport Proteins / chemistry
  • Cation Transport Proteins / isolation & purification
  • Cation Transport Proteins / toxicity*
  • Cats
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Lung / drug effects
  • Male
  • Mass Spectrometry
  • Membrane Potential, Mitochondrial / drug effects
  • Microscopy, Fluorescence
  • Nuclear Magnetic Resonance, Biomolecular
  • Polyenes / chemistry
  • Polyenes / isolation & purification
  • Polyenes / toxicity*
  • Rats
  • Sperm Motility / drug effects
  • Sus scrofa
  • Toxicity Tests

Substances

  • Amino Acids
  • Bacterial Toxins
  • Cation Transport Proteins
  • Polyenes
  • Adenosine Triphosphate