Silver nanoparticles induce a triclosan like antibacterial action mechanism in multi-drug resistant Klebsiella pneumoniae

Infections associated with antimicrobial-resistant (AMR) bacteria now represent a significant threat to human health using conventional therapy. Since AMR bacterial infections are poised to overtake cancer as the main cause of death by 2050, scientists are exploring the efficacy of novel antimicrobial strategies, such as use of silver nanoparticles (Ag NPs) to combat infections. Whilst Ag NPs may hold therapeutic promise, their mode of action on the bacteria remains to be elucidated. In this study, lysozyme coated Ag NPs were synthesized and characterized by TEM-EDS, XRD, UV-vis, FTIR spectroscopy, zeta potential and oxidative potential assay. Ag NPs with an average diameter of 5.2 {+/-} 1.2 nm were found to be bactericidal against multi-drug resistant Klebsiella pneumoniae MGH78578. Deep level transcriptional analysis using RNA sequencing revealed that Ag NPs induced a triclosan-like bactericidal mechanism. RNAseq data showed that Ag NPs were responsible for the inhibition of the type II fatty acid biosynthesis. Additionally, released Ag+ generated oxidative stress both extra- and intracellularly in K. pneumoniae. We show that triclosan-like activity and oxidative stress cumulatively underpinned the antibacterial activity of Ag NPs. This result was confirmed by the analysis of the bactericidal effect of Ag NPs against the isogenic K. pneumoniae MGH78578{Delta} soxS mutant, which exhibits a compromised oxidative stress response compared to the wild type. Here we provide evidence to extend our understanding of the anti-Klebsiella activity associated with silver nanoparticles. This allowed us to model how bacteria might develop resistance against silver nanoparticles, should the latter be used in therapy. Significance StatementMany pathogens including Klebsiella pneumoniae have evolved to become resistance to antimicrobial agents, necessitating the development of alternate and more effective antibacterial compounds. Silver nanoparticles have been proposed as potential antimicrobial agents. However, a complete understanding of the antimicrobial activity of silver nanoparticles is required before these molecules can be used in therapy. Here, we used biochemical assays and RNA sequencing to decipher how silver nanoparticles exert their antibacterial action against multi-drug resistant K. pneumoniae MGH78578. We observed that silver nanoparticles behave similarly with another antimicrobial agent, triclosan. This unique observation provides some clues about how bacteria respond to exposure with silver nanoparticles.