The Antimicrobial Characterization Of N,N’-Bis-Substituted Triazolium Salts Against Eskape Pathogens

Julie A. Wilson


Bacterial infections pose a significant threat to immunocompromised patients, particularly those who are undergoing chemotherapy. This prompts the development of cancer therapeutics that also exhibit effective antimicrobial activities. Increasing multi-drug resistance (MDR) in multiple bacterial species, specifically ESKAPE pathogens, increase the importance of these therapeutic alternatives, as traditional antibacterial treatments are proving to be ineffective or dangerous to patient health. In this study, we examined the bacteriostatic and bactericidal effects of a series of triazolium salt derivatives with a collection of representative bacterial pathogens including Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecium, and an MDR clinical isolate of Acinetobacter baumannii. We characterized bacteriostatic and bactericidal effects of the derivatives as well as their cytotoxicity. All derivatives exhibited variable activity against pathogens, with compounds containing the 1,2,3-triazole parent having a stronger bacteriostatic effect than those containing the 1,2,4-triazole or benzotriazole parent. Furthermore, derivatives containing the 1,2,3-triazole parent consistently exhibited bactericidal effects against all pathogens except A. baumannii while the remainder varied based on the attached substituents. Overall, the methylnaphthyl substituent appears to be a significant moiety that warrants further investigation as it maintains the strongest bacteriostatic and bactericidal effects against pathogens across all parents. Additionally, all of the compounds were found have low hemolytic activity in human red blood cells. Further studies must be done to elucidate the value of these alternative treatments, but the results suggest that ESKAPE pathogen susceptibility to triazolium salt derivatives may result in novel therapeutics to prevent these infections in immunocompromised patients.