Antibacterial Activity of Non-Cytotoxic, Amino Acid-Modified Polycationic Dendrimers against Pseudomonas aeruginosa and Other Non-Fermenting Gram-Negative Bacteria

Abstract

Due to the rapid increase of antimicrobial resistance with ensuring therapeutic failures, the purpose of this study was to identify novel synthetic molecules as alternatives to conventional available, but presently ineffective antibiotics. Variously structured cationic dendrimers previously reported have provided promising outcomes. However, the problem of their cytotoxicity towards eukaryotic cells has not been completely overcome. We have now investigated the antibacterial activities of three not cytotoxic cationic dendrimers (G5Ds: G5H, G5K, and G5HK) against several multidrug-resistant (MDR) clinical strains. All G5Ds displayed remarkable activity against MDR non-fermenting Gram-negative species such as P. aeruginosa, S. maltophilia, and A. baumannii (MICs = 0.5–33.2 µM). In particular, very low MIC values (0.5–2.1 µM) were observed for G5K, which proved to be more active than the potent colistin (2.1 versus 3.19 µM) against P. aeruginosa. Concerning its mechanism of action, in time-killing and turbidimetric studies, G5K displayed a rapid non-lytic bactericidal activity. Considering the absence of cytotoxicity of these new compounds and their potency, comparable or even higher than that provided by the dendrimers previously reported, G5Ds may be proposed as promising novel antibacterial agents capable of overcoming the alarming resistance rates of several nosocomial non-fermenting Gram-negative pathogens.