title: Inhibitory potential of strepthonium A against Shiga toxin production in enterohemorrhagic Escherichia coli (EHEC) strain EDL933.
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.
authors.affiliation: a Department of Botany II, Julius-von-Sachs Institute for Biological Sciences , University of Würzburg , Würzburg , Germany.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: b Institute for Molecular Infection Biology , University of Würzburg , Würzburg , Germany.
authors.forename: Srikkanth
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: c Department of Pharmaceutical Biology , Julius-von-Sachs Institute for Biological Sciences, University of Würzburg , Würzburg , Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Fekete
authors.affiliation: c Department of Pharmaceutical Biology , Julius-von-Sachs Institute for Biological Sciences, University of Würzburg , Würzburg , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krischke
authors.affiliation: c Department of Pharmaceutical Biology , Julius-von-Sachs Institute for Biological Sciences, University of Würzburg , Würzburg , Germany.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Mueller
authors.affiliation: d GEOMAR Helmholtz Centre for Ocean Research, RD3 Marine Microbiology, and Christian-Albrechts University of Kiel , Kiel , Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hentschel
authors.affiliation: b Institute for Molecular Infection Biology , University of Würzburg , Würzburg , Germany.
authors.forename: Tobias A
authors.initials: TA
authors.lastname: Oelschlaeger
authors.affiliation: a Department of Botany II, Julius-von-Sachs Institute for Biological Sciences , University of Würzburg , Würzburg , Germany.
authors.forename: Usama Ramadan
authors.initials: UR
authors.lastname: Abdelmohsen
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D054324:Enterohemorrhagic Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D022621:Shiga Toxin / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D022621:Shiga Toxin
keywords: Drug discovery; EHEC infection; Shiga toxin; Streptomyces