Treating urinary tract infections due to MDR E. coli with Isothiocyanates – a phytotherapeutic alternative to antibiotics?

Abstract

BackgroundMultidrug-resistant (MDR) bacteria are increasingly causing urinary tract infections (UTI), which has been linked to frequent use of antibiotics. Alternative treatment regimens are urgently needed and natural isothiocyanates (ITC) may represent one. ITCs are natural plant products found in nasturtium (Tropaeoli majoris herba) and horseradish (Armoraciae rusticanae radix). PurposeThe objectives were to (1) assess the antimicrobial effects of nature-identical ITCs for UTI treatment caused by uropathogenic E. coli (UPEC), (2) to evaluate a potential influence of antimicrobial resistance on ITC susceptibility, and (3) to test whether ITCs affect UPEC penetration into human uroepithelial cells. MethodsWe tested 217 clinical UPEC isolates, 54.5% of which were classified as MDR, for susceptibility against ITCs. ITC susceptibility testing was performed by broth dilution using a mixture of three synthetic ITCs. Internalization was tested using human T-24 bladder carcinoma cells in an internalization assay co-incubated with UPEC (n = 5) and ITCs. ResultsThe mean minimal inhibitory concentration (MIC) 90 was 0.17 mg/ml, showing very high susceptibility against ITCs. Interestingly, MDR E. coli were significantly less susceptible than non-MDR strains (p = .01). Internalization of UPEC was decreased by 31.9% in the mean when treated with ITCs. Overall, ITCs exerted a strong antimicrobial activity against clinical UPEC isolates and reduced internalization into uroepithelial cells. ConclusionITCs might present a promising treatment alternative for UTIs, expressing both high antimicrobial activity as well as blocking the pathogenic process of human cell penetration by UPEC. Clinical studies, however, are needed to confirm activity of ITCs in UTIs in vivo.