Combating antimicrobial resistance: a closer look at disrupting Escherichia coli metabolism and motility with biogenic silver nanoparticles

Abstract

Antimicrobial resistance (AMR) poses a dire global threat, with bacterial resistance predicted to cause 10 million deaths annually by 2050 if left unaddressed. Among the leading contributors, Escherichia coli ranks as a critical priority pathogen, driving the need for innovative strategies to combat resistance. This study addresses the urgent demand by exploring the antibacterial efficacy and mode of action of biogenic silver nanoparticles (AgNPs) synthesized using Emblica officinalis. AgNPs, characterized as spherical (average size: 46.5 nm) with high stability (zeta potential: -39.02 mV) and photoluminescent properties, exhibited potent antimicrobial activity, with minimum inhibitory concentrations ranging from 9.76 to 19.53 ppm. RNA-seq analysis revealed substantial metabolic and regulatory shifts in E. coli upon AgNP exposure, including upregulation of arginine biosynthesis, metabolism, and transport genes (e.g., argC, argB, argA, artJ), which supported ATP production via the Arginine Deiminase (ADI) pathway and enhanced stress resilience through polyamine synthesis. Upregulation of carA showed the interconnectedness of arginine and pyrimidine biosynthesis under energy-depleted conditions. Simultaneously, downregulation of motility-related genes (flhDC, fliC) disrupted flagellar biosynthesis, rendering E. coli non-motile and more vulnerable to oxidative stress. This was linked to reduced cAMP-CRP complex activity and arginine-sodium competition at flagellar motors. Structural analyses confirmed a face-centered cubic crystalline structure and functionalization with biomolecules, enhancing biocompatibility. Cytotoxicity assays on MDA-MB-231 cells demonstrated dose-dependent reductions in cell viability, with manageable safety profiles. These findings highlight biogenic AgNPs as eco-friendly, effective antimicrobial agents exploiting bacterial metabolic disruption and impaired motility to counter resistance, offering promising solutions to mitigate the AMR crisis.

Keywords: Escherichia coli; Antimicrobial resistance; Arginine biosynthesis; Biogenic silver nanoparticles; Flagella motility.