Antimicrobial activity of amphiphilic neamine derivatives: Understanding the mechanism of action on Gram-positive bacteria

In this study, we have assessed its mechanism of action against Gram-positive bacteria, S. aureus and B. subtilis. By time killing curves, we assessed the bactericidal effect induced by 3′,6-dinonyl neamine on S. aureus MSSA and MRSA. By measuring the displacement of BODIPY™-TR cadaverine bound to lipoteichoic acids (LTA), we showed that 3′,6-dinonyl neamine interacts with these bacterial surface components. We also highlighted the ability of 3′,6-dinonyl neamine to enhance membrane depolarization and induce membrane permeability, by using fluorescent probes, DiSC3C(5) and propidium iodide, respectively. These effects are observed for both MSSA and MRSA S. aureus as well as for B. subtilis. By electronic microscopy, we imaged the disruption of membrane integrity of the bacterial cell wall and by fluorescence microscopy, we demonstrated changes in the localization of lipids from the enriched-septum region and the impairment of the formation of septum. At a glance, we demonstrated that 3′,6-dinonyl neamine interferes with multiple targets suggesting a low ability of bacteria to acquire resistance to this agent. In turn, the amphiphilic neamine derivatives are promising candidates for development as novel multitarget therapeutic antibiotics.Graphical abstract

Source: Biochimica et Biophysica Acta (BBA) Biomembranes - May 31, 2019 Category: Biochemistry Source Type: research