Inhibitory potential of strepthonium A against Shiga toxin production in enterohemorrhagic Escherichia coli (EHEC) strain EDL933

Nat Prod Res. 2017 Dec;31(23):2818-2823. doi: 10.1080/14786419.2017.1297443. Epub 2017 Mar 13.

Abstract

The production of shiga toxin (Stx) is a critical step in the establishment and progress of enterohemorrhagic Escherichia coli (EHEC) infections. The possible release of Stx from dead and dying bacteria, and the risk of resistance development have restricted the usage of antibiotics against EHEC. The chlorinated quaternary ammonium compound, strepthonium A, was isolated from the culture of Streptomyces sp. SBT345 that was cultivated from the Mediterranean sponge Agelas oroides. The structure was elucidated and confirmed by spectroscopic analyses including 1D and 2D NMR, ESI-HRMS, as well as ESI-HRMS2. Strepthonium A follows Lipinski's rule of five with respect to its molecular weight, CLogP values and the number of hydrogen acceptors and donors. Verotoxin ELISA assay demonstrated that Strepthonium A reduced the Stx production in EHEC strain EDL933 at 80 μM concentration without growth inhibition. This study demonstrates the potential of strepthonium A in restraining the production of Stx in EHEC infections.

Keywords: Drug discovery; EHEC infection; Shiga toxin; Streptomyces.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Enterohemorrhagic Escherichia coli / drug effects*
  • Enterohemorrhagic Escherichia coli / growth & development
  • Enterohemorrhagic Escherichia coli / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Shiga Toxin / metabolism*
  • Streptomyces / metabolism*

Substances

  • Anti-Bacterial Agents
  • Shiga Toxin