As the field of nanomedicine emerges, there is a lag in research surrounding the topic of nanoparticle (NP) toxicity, particularly concerned with mechanisms of action. The continuous emergence of bacterial resistance has challenged the research community to develop novel antibiotic agents. Metal NPs are among the most promising of these because show strong antibacterial activity. This review summarizes and discusses proposed mechanisms of antibacterial action of different metal NPs. These mechanisms of bacterial killing include the production of reactive oxygen species, cation release, biomolecule damages, ATP depletion, and membrane interaction. Finally, a comprehensive analysis of the effects of NPs on the regulation of genes and proteins (transcriptomic and proteomic) profiles is discussed.

https://link.springer.com/content/pdf/10.1186/s12951-017-0308-z.pdf

Metal nanoparticles: understanding the mechanisms behind antibacterial activity.

Protein phosphorylation is estimated to affect 30% of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.

Global Analysis of Protein Phosphorylation in Yeast

Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.

/pdf/metal-based-nanoparticles-as-antimicrobial-agents-an-y9sfybpk7p.pdf

Metal-based nanoparticles as antimicrobial agents: an overview.

Since discovery of the first antibiotic drug, penicillin, in 1928, a variety of antibiotic and antimicrobial agents have been developed and used for both human therapy and industrial applications. However, excess and uncontrolled use of antibiotic agents has caused a significant growth in the number of drug resistant pathogens. Novel therapeutic approaches replacing the inefficient antibiotics are in high demand to overcome increasing microbial multidrug resistance. In the recent years, ongoing research has focused on development of nano-scale objects as efficient antimicrobial therapies. Among the various nanoparticles, silver nanoparticles have gained much attention due to their unique antimicrobial properties. However, concerns about the synthesis of these materials such as use of precursor chemicals and toxic solvents, and generation of toxic byproducts have led to a new alternative approach, green synthesis. This eco-friendly technique incorporates use of biological agents, plants or microbial agents as reducing and capping agents. Silver nanoparticles synthesized by green chemistry offer a novel and potential alternative to chemically synthesized nanoparticles. In this review, we discuss the recent advances in green synthesis of silver nanoparticles, their application as antimicrobial agents and mechanism of antimicrobial mode of action.

https://pubs.rsc.org/en/content/articlepdf/2019/ra/c8ra08982e

Green synthesis of silver nanoparticles: biomolecule-nanoparticle organizations targeting antimicrobial activity

The green synthesis of nanoparticles (NPs) using living cells is a promising and novelty tool in bionanotechnology. Chemical and physical methods are used to synthesize NPs; however, biological methods are preferred due to its eco-friendly, clean, safe, cost-effective, easy, and effective sources for high productivity and purity. High pressure or temperature is not required for the green synthesis of NPs, and the use of toxic and hazardous substances and the addition of external reducing, stabilizing, or capping agents are avoided. Intra- or extracellular biosynthesis of NPs can be achieved by numerous biological entities including bacteria, fungi, yeast, algae, actinomycetes, and plant extracts. Recently, numerous methods are used to increase the productivity of nanoparticles with variable size, shape, and stability. The different mechanical, optical, magnetic, and chemical properties of NPs have been related to their shape, size, surface charge, and surface area. Detection and characterization of biosynthesized NPs are conducted using different techniques such as UV-vis spectroscopy, FT-IR, TEM, SEM, AFM, DLS, XRD, zeta potential analyses, etc. NPs synthesized by the green approach can be incorporated into different biotechnological fields as antimicrobial, antitumor, and antioxidant agents; as a control for phytopathogens; and as bioremediative factors, and they are also used in the food and textile industries, in smart agriculture, and in wastewater treatment. This review will address biological entities that can be used for the green synthesis of NPs and their prospects for biotechnological applications.

Green Synthesis of Metallic Nanoparticles and Their Prospective Biotechnological Applications: an Overview

Zinc oxide nanoparticles: Synthesis, antiseptic activity and toxicity mechanism.

Zearalenone and its metabolites: Effect on human health, metabolism and neutralisation methods.

Background/Purpose In this study, an acidophilic actinobacteria strain was used as a novel reducing agent for a single-step synthesis of nanostructure silver particles. We used a Streptacidiphilus durhamensis HGG16n isolate for efficient synthesis of bioactive silver nanoparticles [bio(AgNPs)] in an inexpensive, eco-friendly, and nontoxic manner. The obtained bio(AgNPs) exhibited unique physicochemical and biochemical properties. Methods Structural, morphological, and optical properties of the synthesized biocolloids were characterized by spectroscopy, dynamic light scattering, and electron microscopy approaches. The antimicrobial activity was evaluated using the well- and disc-diffusion methods. Results The obtained crystalline structure and stable biosynthesized silver nanoparticles ranged in size from 8 nm to 48 nm and were mostly spherical in shape. Antimicrobial assays of the silver nanoparticles against pathogenic bacteria showed the highest antimicrobial activity against Pseudomonas aeruginosa , Staphylococcus aureus , and Proteus mirabilis, followed by Escherichia coli , Klebsiella pneumoniae , and Bacillus subtilis . Moreover, the synergistic effect of bio(AgNPs) with various commercially available antibiotics was also evaluated. Conclusion These results provide insight into the development of new antimicrobial agents along with synergistic enhancement of the antibacterial mechanism against clinical bacteria.

Paweł Pomastowski

Papers

Zinc oxide nanoparticles: Synthesis, antiseptic activity and toxicity mechanism.

Zearalenone and its metabolites: Effect on human health, metabolism and neutralisation methods.

Antimicrobial activity of biosilver nanoparticles produced by a novel Streptacidiphilus durhamensis strain

Silver nanoparticles: Synthesis, investigation techniques, and properties.

Medicago sativa as a source of secondary metabolites for agriculture and pharmaceutical industry