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.
Highlights
Among numerous toxins secreted by intestinal pathogens, Shiga toxins are ones of best described toxins that cause severe symptoms, including hemolytic colitis
To evaluate their effects on bacterial growth the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), as well as the zone inhibition diameter were assessed for the clinical isolates O157:H7strains: CB571, 86–24 and wild type E. coli MG1655 strain
We observed that the growth inhibition varied for different ITCs, with the most potent effect of benzyl isothiocynanate (BITC) which was evident already at 1/128 minimum inhibitory concentrations (MIC) while the growth arrest during first hours of cultivation was observed at 1/32 MIC or other tested ITCs, higher concentrations were necessary to obtain full growth arrest at the exponential growth phase, e.g. 1/16 for SFN and allyl isothiocyanate (AITC), 1/4 for phenyl isothiocyanate (PITC) or 1/2 for isopropyl isothiocyanate (IPRITC) (Fig. 2B)
Summary
Among numerous toxins secreted by intestinal pathogens, Shiga toxins are ones of best described toxins that cause severe symptoms, including hemolytic colitis. As we previously demonstrated, one of the representatives of isothiocyanates (ITC), phenetyl ITC (PEITC), could inhibit growth of EHEC strains harboring stx genes and at the same time did not lead to the prophage induction and Shiga toxin production[15]. It was proposed that PEITC-mediated induction of the stringent response was responsible for inhibition of bacterial growth accompanied by inhibition of prophage induction and development, and Shiga toxin synthesis[15] These findings put PEITC among the potential antimicrobial factors, especially in infections with pathogens when the standard antibiotic therapy is not advisable. The aim of this work was to compare activities of isothiocyanates differing in the structure of the alkyl/aryl group towards STEC strains, in particular their influence on bacterial growth, Shiga toxin-converting prophage induction, and expression of the stx genes, and to elucidate the mechanism of their activity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
