International Journal of Nanomedicine (Feb 2019)

Antibacterial activity and mechanism of silver nanoparticles against multidrug-resistant Pseudomonas aeruginosa

  • Liao S,
  • Zhang Y,
  • Pan X,
  • Zhu F,
  • Jiang C,
  • Liu Q,
  • Cheng Z,
  • Dai G,
  • Wu G,
  • Wang L,
  • Chen L

Journal volume & issue
Vol. Volume 14
pp. 1469 – 1487

Abstract

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Shijing Liao,1,* Yapeng Zhang,1,* Xuanhe Pan,1 Feizhou Zhu,2 Congyuan Jiang,3 Qianqian Liu,2 Zhongyi Cheng,4 Gan Dai,1 Guojun Wu,1 Linqian Wang,5 Liyu Chen1 1Department of Medical Microbiology, School of Basic Medical Sciences, Central South University, Changsha 410013, China; 2Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha 410013, China; 3Hunan Anson Biotechnology Co., Ltd., Changsha 410008, China; 4Jingjie PTM BioLab Co., Ltd., Hangzhou Economic and Technological Development Area, Hangzhou 310018, China; 5Department of Clinical Laboratory, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China *These authors contributed equally to this work Background: The threat of drug-resistant Pseudomonas aeruginosa requires great efforts to develop highly effective and safe bactericide. Objective: This study aimed to investigate the antibacterial activity and mechanism of silver nanoparticles (AgNPs) against multidrug-resistant P. aeruginosa. Methods: The antimicrobial effect of AgNPs on clinical isolates of resistant P. aeruginosa was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). In multidrug-resistant P. aeruginosa, the alterations of morphology and structure were observed by the transmission electron microscopy (TEM); the differentially expressed proteins were analyzed by quantitative proteomics; the production of reactive oxygen species (ROS) was assayed by H2DCF-DA staining; the activity of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) was chemically measured and the apoptosis-like effect was determined by flow cytometry. Results: Antimicrobial tests revealed that AgNPs had highly bactericidal effect on the drug-resistant or multidrug-resistant P. aeruginosa with the MIC range of 1.406–5.625 µg/mL and the MBC range of 2.813–5.625 µg/mL. TEM showed that AgNPs could enter the multidrug-resistant bacteria and impair their morphology and structure. The proteomics quantified that, in the AgNP-treated bacteria, the levels of SOD, CAT, and POD, such as alkyl hydroperoxide reductase and organic hydroperoxide resistance protein, were obviously high, as well as the significant upregulation of low oxygen regulatory oxidases, including cbb3-type cytochrome c oxidase subunit P2, N2, and O2. Further results confirmed the excessive production of ROS. The antioxidants, reduced glutathione and ascorbic acid, partially antagonized the antibacterial action of AgNPs. The apoptosis-like rate of AgNP-treated bacteria was remarkably higher than that of the untreated bacteria (P<0.01). Conclusion: This study proved that AgNPs could play antimicrobial roles on the multidrug-resistant P. aeruginosa in a concentration- and time-dependent manner. The main mechanism involves the disequilibrium of oxidation and antioxidation processes and the failure to eliminate the excessive ROS. Keywords: silver nanoparticles, AgNPs, antibacterial activity, mechanism, Pseudomonas aeruginosa, multidrug-resistant bacterium

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