Nowicki Dariusz, Rodzik Olga, Herman-Antosiewicz Anna, Szalewska-Pałasz Agnieszka
Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
Sci Rep. 2016 Feb 29;6:22263. doi: 10.1038/srep22263.
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.
肠出血性大肠杆菌（EHEC）产生的志贺毒素是这些菌株致病性的原因，它与宿主基因组中存在的λ噬菌体的诱导、噬菌体DNA的复制以及stx基因的表达密切相关。对EHEC感染进行抗生素治疗可能会导致原噬菌体诱导进入裂解发育阶段，从而增加严重并发症的风险。这与多重耐药性的传播一起，增加了对新型抗菌剂的需求。我们在此报告，异硫氰酸盐（ITC），即植物次生代谢产物，如萝卜硫素（SFN）、烯丙基异硫氰酸酯（AITC）、苄基异硫氰酸酯（BITC）、苯基异硫氰酸酯（PITC）和异丙基异硫氰酸酯（IPRITC），可抑制携带stx的原噬菌体的细菌生长和裂解发育。ITC抗菌作用的潜在机制涉及诱导全局细菌应激调节系统，即严紧反应。其警报素鸟苷五磷酸/四磷酸（（p）ppGpp）影响主要的细胞过程，包括核酸合成，这导致对原噬菌体诱导和毒素合成的有效抑制，从而消除EHEC对人和猿猴细胞的毒力。因此，ITC可被视为EHEC感染的潜在治疗剂。
