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.

Antibiotic and Antibiofilm Activities of Salvadora persica L. Essential Oils against Streptococcus mutans: A Detailed Comparative Study with Chlorhexidine Digluconate

“…The increased expression of sodA gene shows that exposure to the tested essential oils induces oxidative stress in S. mutans. Studies have demonstrated that isothiocynates can cause general stress in E. coli, as evidenced by the increased concentration of general stress regulator molecule guanosine penta/tetraphosphate ((p)ppGpp) [23]. Biofilm formation by oral pathogens is one of the most important traits contributing to their pathogenicity [19,24,25].…”

Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections

“…However, another related compound, nitroscanate, is widely employed in veterinary medicine to treat roundworm, hookworm and tapeworms [ 33 ]. Currently, the isothiocyanates are researched for activity against intestinal bacteria and cancer [ 34 , 35 ].…”

Isothiocyanates: An Overview of Their Antimicrobial Activity against Human Infections

“…The strains of E. coli that produce Stx (STEC), such as E. coli O157: H7, have been studied extensively [ 88 ]. ITCs are currently considered as potential therapeutic agents against EHEC infections [ 45 ].…”

“…Recently, Nowicki et al showed that BITC was more effective than AITC in the inhibition of EHEC E. coli growth [ 45 ]. The study was performed comparing the antibacterial activity of synthetic SFN, AITC, BITC, phenyl ITC (PITC) and isopropyl ITC (IPRITC) against different clinical and laboratory EHEC E. coli strains, including WT ( E. coli MG1655) and Shiga toxin-producing E. coli (O157:H7 E. coli) .…”