TY - JOUR
T1 - Mutagenesis and Resistance Development of Bacteria Challenged by Silver Nanoparticles
AU - Wu, Kun
AU - Li, Haichao
AU - Cui, Xiao
AU - Feng, Ruobing
AU - Chen, Weizhe
AU - Jiang, Yuchen
AU - Tang, Chao
AU - Wang, Yaohai
AU - Wang, Yan
AU - Shen, Xiaopeng
AU - Liu, Yufei
AU - Lynch, Michael
AU - Long, Hongan
N1 - Funding Information:
This work is supported by the National Natural Science Foundation of China (31961123002, 31872228), The Fundamental Research Funds for the Central Universities of China (202041001), The Young Taishan Scholars Program of Shandong Province (tsqn201812024), and National Institutes of Health award (R35-GM122566).
Funding Information:
This work is supported by the National Natural Science Foundation of China (31961123002, 31872228), The Fundamental Research Funds for the Central Universities of China (202041001), The Young Taishan Scholars Program of Shandong Province (tsqn201812024), and National Institutes of Health award (R35-GM122566). We appreciate the technical help from Vazyme Biotech Co., Ltd., Nanjing, and Wei Yang, OUC. We also thank the following undergraduate students for helping with experiments: Wenlu Zhang, An Jiang, Xia Zhou, Huilin Guo, Xiang Li, Dange Zhao, Chenchen Ruan, Xiaokai Fan, Weijian Huang, Dan Liu, Hui Li, Zehua Niu, Yuanyuan Zhang, Jiao Pan, Dapeng Ran, Xiaomeng Hu, Chengjing Zhang, and Jiyuan Hou. We also thank Xue Wang and Xiaoying Bian for kindly providing plasmids for gene knockout. All bioinformatic analyses were performed with IEMB-1 computation clusters at OUC. Kun Wu and Hongan Long designed the study; Kun Wu, Haichao Li, Yaohai Wang, Xiao Cui, Ruobing Feng, Weizhe Chen, Yuchen Jiang, and Chao Tang performed experiments and data analyses; Kun Wu, Hongan Long, Michael Lynch, Yufei Liu, Xiaopeng Shen, and Yan Wang wrote the manuscript. All authors read and approved the manuscript before submission. We declare that we have no competing interests.
Publisher Copyright:
Copyright © 2022 Wu et al.
PY - 2022/10
Y1 - 2022/10
N2 - 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 coli. 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.
AB - 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 coli. 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.
KW - antimicrobial agents
KW - drug resistance
KW - environmental mutagenesis
KW - experimental evolution
KW - metallic nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85140206776&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85140206776&partnerID=8YFLogxK
U2 - 10.1128/aac.00628-22
DO - 10.1128/aac.00628-22
M3 - Article
C2 - 36094196
AN - SCOPUS:85140206776
SN - 0066-4804
VL - 66
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 10
ER -