# Isothiocyanates: An Overview of Their Antimicrobial Activity against Human Infections
## 4 Isothiocyanates Antimicrobial Properties against Human Pathogens
### Pseudomonas Aeruginosa
aeruginosa_ characterized to show from two to six times greater ability to produce biofilms and resistant phenotypes [48]. Tests were also performed using a mixture (38% (_v/v_) AITC, 50% BITC and 12% PEITC) indicating as ITCM. The results showed that AITC was the most effective ITCs against the _P. aeruginosa_ clinical isolate, followed by the ITCM mixture, by the BITC and finally by PEITC. Subsequently AITC, BITC, PEITC and the ITCM mixture were used to test their ability to inhibit biofilm production. Results indicated that PEITC (at a concentration of 500 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) caused a significant reduction in the biofilm development of _P. aeruginosa_ (native biofilm formation of 1.02 \(\pm\) 0.04 versus 0.62 \(\pm\) 0.05 under the influence of PEITC) and only 100 \(\mathrm{\SIUnitSymbolMicro g}\)/mL of the ITCM mixture were sufficient to achieve similar result (1.02 \(\pm\) 0.04 of native biofilm formation versus 0.69 \(\pm\) 0.06 in treatment with the mixture). BITC and AITC did not show inhibitory effect on biofilm production. To the contrary, AITC was the most effective ITC (concentrations ranging between 200 and 800 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) against _P. aeruginosa_ strains into the mature biofilm followed by BITC (concentrations from 250 to 1000 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) and finally by ITCM mixture (concentrations from 500 to 1000 \(\mathrm{\SIUnitSymbolMicro g}\)/mL). The less effective ITC was the PEITC in contrast to what observed for _P. aeruginosa_ strains during biofilm development [48]. Moreover it has been observed that ITCM exposure induced the killing of bacteria into the mature biofilm without restriction to biofilm permeation, one of the most critical point for the effectiveness of any antimicrobial agent used against mature bacterial biofilm. These are interesting finding because anti-biofilm compound that show both the ability to prevent biofilm formation and the ability to inhibit metabolic activity within established biofilms are rare. Moreover seems to be no such diffusion barrier for the tested ITC compounds as suggested by the authors. The authors also reported a synergistic effect combining the ITCM mixture with meropenem against biofilms produced by carbapenem-susceptible _P. aeruginosa_ clinical isolates. Interestingly meropenem alone was more efficient than ITC mixture to killing planktonic bacteria but only when combined with ITCM mixture it was possible to observe an substantial reduction of carbapenem-susceptible _P. aeruginosa_ metabolic activity into the biofilm. In contrast, no synergistic effect of meropenem and ITCM mixture on biofilms produced by carbapenem resistant _P. aeruginosa_ strains was observed [48]. The antimicrobial effects of these ITCs on _P. aeruginosa_ growth has been recently investigated by [PERSON] et al. [49]. The authors tested the effect of AITC and PEITC against _P. aeruginosa_ ATCC 10145 strain. Results indicated that AITC (MIC = 100 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) and PEITC (MIC = 100 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) were capable of altering the integrity of the bacterial cell membrane in a dose-dependent manner. In addition the treatment with AITC and PEITC determined an increase in the hydrophilic character of the membrane, thereby changing the physico-chemical characteristics of the bacterial membrane [49]. Although these results indicated that ITCs antibacterial activity against _P. aeruginosa_ occurred by alterations of cell membrane, this evidence did not explain the mechanism of action against _P. aeruginosa_ strains. An alternative strategy to suppress the growth of _P. aeruginosa_ lies in inhibition of the bacterial quorum sensing (QS). Concerning this evidence [PERSON] et al [44] investigated about the ability of synthetic SFN and ERN to activate or interfere with the _las_ and _rhl_ QS systems of _P. aeruginosa_. Results indicated that SFN and ERN were shown to inhibit bacterial quorum detection. The _P.