The antimicrobial activity of nanoparticles: present situation and prospects for the future

Abstract

Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed.

Keywords: antimicrobial activity; antimicrobial resistance; nanoparticles; oxidative stress.

Figure 1

The antibacterial application of NPs. Abbreviation: NPs, nanoparticles.

Figure 2

Bactericidal activity of NDs. Notes: (A) TEM images indicate that, at sublethal ND concentrations of 0.5 mg/L, ND- is incorporated into E. coli cells and seems to deform the cellular shape (a, b); ND+ seems mainly to bind to cellular surface structures (c, d); Similar to ND-, agglomerates of negatively charged ND_pure− are also found inside the cells, but they do not alter bacterial morphology (e, f); showing similar cell shapes to the ND-free control of E. coli (g, h). (B) Grades and pretreatments of NDs: a, negatively charged ND- and ND_raw/ND_{raw n.u.} were shown to exhibit strong antibacterial properties under aqueous conditions, while ND+ caused bacterial death only at high ND concentrations; b, ND_pure, independent of their charge, did not show any bactericidal effects. (C) Antibacterial activity of NDs on E. coli and B. subtilis. (a,b) Negatively charged ND- and ND_raw/ND_{raw n.u.} strongly decreased bacterial viability measured by ATP levels in 15 min, while positively charged ND+ decrease ATP levels only at the highest ND concentrations for Gram-negative E. coli (a) and Gram-positive B. subtilis (b); (c) After incubation with 500 mg/L NDs, the determination of colony-forming units for E. coli and B. subtilis led to similar trends to the measurement of ATP, indicating that ND- and ND_raw/ND_{raw n.u.} are very effective at inhibiting bacterial growth, while positively charged ND+ are less bactericidal. Reprinted with permission from Wehling J, Dringen R, Zare R, Mass M, Rezwan K. Bactericidal activity of partially oxidized nanodiamonds. ACS Nano. 2014;8(6):6475–6483. Copyright 2014 American Chemical Society. Abbreviations: B. subtilis, Bacillus subtilis; CFU, colony-forming unit; E. coli, Escherichia coli; ND, nanodiamond; TEM, transmission electron microscopy; n.u, no ultrasonication.

Figure 2

Bactericidal activity of NDs. Notes: (A) TEM images indicate that, at sublethal ND concentrations of 0.5 mg/L, ND- is incorporated into E. coli cells and seems to deform the cellular shape (a, b); ND+ seems mainly to bind to cellular surface structures (c, d); Similar to ND-, agglomerates of negatively charged ND_pure− are also found inside the cells, but they do not alter bacterial morphology (e, f); showing similar cell shapes to the ND-free control of E. coli (g, h). (B) Grades and pretreatments of NDs: a, negatively charged ND- and ND_raw/ND_{raw n.u.} were shown to exhibit strong antibacterial properties under aqueous conditions, while ND+ caused bacterial death only at high ND concentrations; b, ND_pure, independent of their charge, did not show any bactericidal effects. (C) Antibacterial activity of NDs on E. coli and B. subtilis. (a,b) Negatively charged ND- and ND_raw/ND_{raw n.u.} strongly decreased bacterial viability measured by ATP levels in 15 min, while positively charged ND+ decrease ATP levels only at the highest ND concentrations for Gram-negative E. coli (a) and Gram-positive B. subtilis (b); (c) After incubation with 500 mg/L NDs, the determination of colony-forming units for E. coli and B. subtilis led to similar trends to the measurement of ATP, indicating that ND- and ND_raw/ND_{raw n.u.} are very effective at inhibiting bacterial growth, while positively charged ND+ are less bactericidal. Reprinted with permission from Wehling J, Dringen R, Zare R, Mass M, Rezwan K. Bactericidal activity of partially oxidized nanodiamonds. ACS Nano. 2014;8(6):6475–6483. Copyright 2014 American Chemical Society. Abbreviations: B. subtilis, Bacillus subtilis; CFU, colony-forming unit; E. coli, Escherichia coli; ND, nanodiamond; TEM, transmission electron microscopy; n.u, no ultrasonication.

Figure 3

The interaction network of differential proteins induced by CuO NPs. Notes: The network was created by the STRING algorithm, and strong interactions are represented by thicker lines. Reprinted from Su Y, Zheng X, Chen Y, Li M, Liu K. Alteration of intracellular protein expressions as a key mechanism of the deterioration of bacterial denitrification caused by copper oxide nanoparticles. Sci Rep. 2015;5:15824. Abbreviation: NPs, nanoparticles.

Figure 4

Mechanisms of NP action in bacteria cells. Notes: NPs can attack bacteria cell through multiple mechanisms: the formation of ROS leading to membrane, protein, and DNA damage; direct interaction occurs with cell membrane because some metal-based NPs can generate metal ion via dissolving, for example, inhibition of electron transport chain; and the regulation of bacterial metabolic processes. Abbreviations: NPs, nanoparticles; ROS, reactive oxygen species.