4.7 Article

Mutagenesis and Resistance Development of Bacteria Challenged by Silver Nanoparticles

Journal

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 66, Issue 10, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/aac.00628-22

Keywords

metallic nanoparticles; antimicrobial agents; drug resistance; experimental evolution; environmental mutagenesis

Funding

  1. National Natural Science Foundation of China [31961123002, 31872228]
  2. Fundamental Research Funds for the Central Universities of China [202041001]
  3. Young Taishan Scholars Program of Shandong Province [tsqn201812024]
  4. National Institutes of Health award [R35-GM122566]

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Silver nanoparticles (AgNPs) have broad-spectrum antimicrobial properties, but their mutagenic effects and resistance mechanisms in bacteria are still controversial. This study found that AgNPs do not accelerate resistance mutation generation by increasing the mutation rate, and they also inhibit quorum sensing in bacteria. However, bacteria can still develop resistance through two-component regulatory systems.
Because of their extremely broad spectrum and strong biocidal power, nanoparticles of metals, especially silver (AgNPs), have been widely applied as effective antimicrobial agents against bacteria, fungi, and so on. However, the mutagenic effects of AgNPs and resistance mechanisms of target cells remain controversial. In this study, we discover that AgNPs do not speed up resistance mutation generation by accelerating genome-wide mutation rate of the target bacterium Escherichia coll. AgNPs-treated bacteria also show decreased expression in quorum sensing (QS), one of the major mechanisms leading to population-level drug resistance in microbes. Nonetheless, these nanomaterials are not immune to resistance development by bacteria. Gene expression analysis, experimental evolution in response to sublethal or bactericidal AgNPs treatments, and gene editing reveal that bacteria acquire resistance mainly through two-component regulatory systems, especially those involved in metal detoxification, osmoregulation, and energy metabolism. Although these findings imply low mutagenic risks of nanomaterial-based antimicrobial agents, they also highlight the capacity for bacteria to evolve resistance.

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