Silver Nanoparticles Induce a Triclosan-Like Antibacterial Action Mechanism in Multi-Drug Resistant Klebsiella pneumoniae.

Vikram Pareek,Stéphanie Devineau,Jitendra Panwar,Shabarinath Srikumar,Séamus Fanning,Arpit Bhargava,Sathesh K Sivasankaran

doi:10.3389/fmicb.2021.638640

Abstract

Infections associated with antimicrobial-resistant bacteria now represent a significant threat to human health using conventional therapy, necessitating the development of alternate and more effective antibacterial compounds. Silver nanoparticles (Ag NPs) have been proposed as potential antimicrobial agents to combat infections. A complete understanding of their antimicrobial activity is required before these molecules can be used in therapy. Lysozyme coated Ag NPs were synthesized and characterized by TEM-EDS, XRD, UV-vis, FTIR spectroscopy, zeta potential, and oxidative potential assay. Biochemical assays and deep level transcriptional analysis using RNA sequencing were used to decipher how Ag NPs exert their antibacterial action against multi-drug resistant Klebsiella pneumoniae MGH78578. RNAseq data revealed that Ag NPs induced a triclosan-like bactericidal mechanism responsible for the inhibition of the type II fatty acid biosynthesis. Additionally, released Ag+ generated oxidative stress both extra- and intracellularly in K. pneumoniae. The data showed 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 ΔsoxS mutant, which exhibits a compromised oxidative stress response compared to the wild type. Silver nanoparticles induce a triclosan-like antibacterial action mechanism in multi-drug resistant K. pneumoniae. This study extends our understanding of anti-Klebsiella mechanisms associated with exposure to Ag NPs. This allowed us to model how bacteria might develop resistance against silver nanoparticles, should the latter be used in therapy.

Highlights

Antimicrobial resistance (AMR) is responsible for approximately 700,000 deaths annually across the globe and this number is expected to increase further if new measures are not adopted and antibacterial compounds discovered (World Health Organization, 2019)
The surface charge of L-antimicrobial strategies using silver nanoparticles (Ag NPs) was estimated by measuring their zeta potential in water and modified Luria Bertani (LB) medium at 37◦C
The 1,632 cm−1 peak in the Fourier Transform Infrared spectroscopy (FTIR) spectrum corresponds to the amide I vibration characteristic of the protein backbone, confirming the presence of lysozyme associated with Ag NPs (Figure 1E) (Baker et al, 2014)

Summary

Introduction

Antimicrobial resistance (AMR) is responsible for approximately 700,000 deaths annually across the globe and this number is expected to increase further if new measures are not adopted and antibacterial compounds discovered (World Health Organization, 2019). Klebsiella pneumoniae is one of the members of the ESKAPE pathogens (representing Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) (Pendleton et al, 2013) It is a member of Enterobacteriaceae family— Gram-negative, non-motile, and rod-shaped. This bacterium is considered an opportunistic pathogen commonly found in the intestine, mouth, and skin of humans It is mainly associated with hospital-acquired infections (nosocomial infections) and responsible for respiratory/urinary tract infections, pneumonia, and sepsis (Podschun and Ullmann, 1998; Lee and Burgess, 2012; World Health Organization, 2019). Novel antibacterial strategies are required to overcome this challenge (Adamo and Margarit, 2018; Mulani et al, 2019)

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