# Isothiocyanates: An Overview of Their Antimicrobial Activity against Human Infections
## 4 Isothiocyanates Antimicrobial Properties against Human Pathogens
### Escherichia coli  
_Escherichia coli_ is the main facultative anaerobic bacterium that lives in the human intestine. Although considered a harmless commensal microorganism, it can be responsible for severe intestinal and extraintestinal infections. Several strains of adapted _E. coli_ have been identified and characterized. New clones have shown the ability to acquire virulence factors that make _E. coli_ able to colonize different human districts and cause a wide range of diseases [86]. The most investigated intestinal pathogenic strain of _E. coli_ is enterohemorrhagic _E. coli_ (EHEC) [87]. The outcome of EHEC infections depends on the production of Shiga toxins (Stx). 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 [PERSON] et al. assessed the antimicrobial property of an extract of _Wasabia japonica_ (Japanese horseradish) containing 59 \(\mathrm{\SIUnitSymbolMicro g}\)/mL of AITC against _E. coli_ O157:H7 (B0241 strain), comparing it with its synthetic analogue. The authors reported that 59 \(\mathrm{\SIUnitSymbolMicro g}\)/mL of natural AITC was sufficient to inhibit _E. coli_ growth up to 12 h of incubation and a similar result was obtained using the synthetic analog, suggesting that AITC is the main ITC responsible for the antimicrobial activity of _Wasabia japonica_[55]. [PERSON] et al. evaluated the antibacterial efficacy of synthetic AITC compared to polymyxin B against _E. coli_ O157: H7 ATCC 43895 strain [56]. Results indicated that synthetic AITC (1.000 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) showed less efficacy than polymyxin B (10 \(\mathrm{\SIUnitSymbolMicro g}\)/mL). Indeed a 100-fold greater amount of AITC was required to exert a similar result as the conventional antibiotic. Moreover, AITC induced its antimicrobial effect on bacterial membranes, leading to leakage of cellular substances and to bacterial death similar to that observed for polymyxin B [56]. Although this experiment suggested that AITC induced its antimicrobial effect on the bacterial membrane, the mechanism of action of AITC against _E. coli_ O157:H7 is still unknown. For this reason [PERSON] and [PERSON] assessed the inhibitory effect of synthetic AITC toward two enzymes having a key role in the bacterial metabolism: thioredoxin reductase, implicated in ribonucleotide synthesis; and acetate kinase, related to energy metabolism [57]. The conclusions reached by the authors indicated that AITC inhibits the level of activity of thioredoxin in a dose-dependent manner. It was hypothesized that AITC may interact with the sulfhydryl groups in the catalytic domain of thioredoxin, inducing inferior enzyme activity that could influence bacterial DNA synthesis. Although less effective, AITC was also able to significantly inhibit acetate kinase activity through the sulfhydryl groups of the enzyme, influencing bacterial energy metabolism [57]. AITC is not the only ITC that has been shown to exert antimicrobial effects against _E. coli_ strains. Indeed [PERSON] et al. reported that ethanolic _Moringa_ leaf extract showed antimicrobial activity against _E. coli_[60]. Subsequently, [PERSON] et al. tested the effectiveness of powdered _Moringa_ leaf juice and leaf extracts (water or ethanol) against _E. coli_ isolated from patients [61]. The results indicated that only the powdered leaf juice had bactericidal efficacy (IZ = 40.45 \(\pm\) 0.37) when compared to the tetracycline control (IZ = 19.03 \(\pm\) 0.44). The water or ethanol extracts showed a lower efficacy compared to powdered leaf juice but they are comparable--fresh leaf aqueous extract IZ = 16.8 \(\pm\) 0.12; ethanol extract IZ = 21 \(\pm\) 0.16--to the conventional antibiotic. Moreover, [PERSON] et al., reported that both synthetic AITC and PEITC were able to affect _Escherichia coli_ CECT 434 with similar effects [49].