title: Isothiocyanates as effective agents against enterohemorrhagic Escherichia coli: insight to the mode of action.
abstract: Production of Shiga toxins by enterohemorrhagic Escherichia coli (EHEC) which is responsible for the pathogenicity of these strains, is strictly correlated with induction of lambdoid bacteriophages present in the host's genome, replication of phage DNA and expression of stx genes. Antibiotic treatment of EHEC infection may lead to induction of prophage into a lytic development, thus increasing the risk of severe complications. This, together with the spread of multi-drug resistance, increases the need for novel antimicrobial agents. We report here that isothiocyanates (ITC), plant secondary metabolites, such as sulforaphane (SFN), allyl isothiocyanate (AITC), benzyl isothiocynanate (BITC), phenyl isothiocyanate (PITC) and isopropyl isothiocyanate (IPRITC), inhibit bacterial growth and lytic development of stx-harboring prophages. The mechanism underlying the antimicrobial effect of ITCs involves the induction of global bacterial stress regulatory system, the stringent response. Its alarmone, guanosine penta/tetraphosphate ((p)ppGpp) affects major cellular processes, including nucleic acids synthesis, which leads to the efficient inhibition of both, prophage induction and toxin synthesis, abolishing in this way EHEC virulence for human and simian cells. Thus, ITCs could be considered as potential therapeutic agents in EHEC infections.
authors.affiliation: Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Nowicki
authors.affiliation: Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Rodzik
authors.affiliation: Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Herman-Antosiewicz
authors.affiliation: Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szalewska-Pałasz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004261:DNA Replication / Q000187:drug effects; D054324:Enterohemorrhagic Escherichia coli / Q000187:drug effects* / Q000502:physiology / Q000821:virology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology*; D039002:Prophages / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D022621:Shiga Toxin / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D017879:Isothiocyanates; D017382:Reactive Oxygen Species; D022621:Shiga Toxin