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bioRxiv · 10.1101/2025.01.28.635224

Molecular evolution of silver nanoparticle resistance in a bacterial pathogen and a unique adaptation response to ionic silver

McNeilly, O.·Mediati, D. G.·Pittorino, M. J.·Mann, R.·Soderstrom, B.·Hamidian, M.·Gunawan, C.
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Abstract

This research explores the adaptive defense mechanisms of a nanosilver-resistant pathogen (NAgR) to protect and fight off the complex antimicrobial targeting of silver nanoparticles. The Gram-negative bacterium Acinetobacter baumannii upregulated expression of outer membrane proteins for cell surface defense, as well as membrane and capsule synthesis genes. Increased abundance of surface-attached biofilm colonies in NAgR was linked to the phenotypically indicated increase in membrane integrity, with the bacterium also forming more EPS, the biopolymer matrix that protects the residing colony. In response to the known reactive oxygen species (ROS) toxicity characteristics of the nanoparticle, NAgR upregulated its oxidative stress management system, specifically involving ROS scavenger enzymes and opportunistic metal efflux pumps. Many of these evolved defense mechanisms only manifested in the resistant bacterium, while they were absent in the wild-type strain. This study also details the unique defenses of an ionic silver-adapted A. baumannii variant, having evolved from the same wild-type parental strain as NAgR. Despite similarities in cell surface and biofilm defense trends, the slower-to-kill tolerant strain (AgT) exclusively upregulated multidrug efflux systems and respiratory chain enzymes, thought to maintain enhanced respiration activity, a known tolerant characteristic. Identification of these stable defense mechanisms can recommend strategies for molecular targeting to overcome the adaptation phenomena.

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McNeilly, O., Mediati, D. G., Pittorino, M. J., Mann, R., Soderstrom, B., Hamidian, M., Gunawan, C.. 2025-01-28. Molecular evolution of silver nanoparticle resistance in a bacterial pathogen and a unique adaptation response to ionic silver. https://doi.org/10.1101/2025.01.28.635224

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