The High Penetrability of Nanoparticles into Bacterial Membranes: A Key of a Potential Application
Online veröffentlicht: 21. März 2023
Seitenbereich: 3 - 11
Eingereicht: 01. Jan. 2021
Akzeptiert: 01. Juni 2021
DOI: https://doi.org/10.2478/am-2023-0001
Schlüsselwörter
© 2023 Amina Meliani et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Furthermore, its survival in the host in the early stages of infection is supported by the secretion of toxins and virulence factors, including pyocyanin and its proteases elastase and alkaline protease (AprA) [49].
It may turn out that recent studies have reported several innovative therapeutic technologies. Research studies have demonstrated pronounced effectiveness in fighting these biofilms, which are responsible for microbial resistance [62] and persistent infections [14]. However, with an acquired resistance to antibiotics or biocides,
The widespread use of broad-spectrum antibiotics has led to the appearance of multidrug-resistant (MDR)
On the other hand, NPs are more toxic to human health in comparison to large-sized particles of the same chemical substance, and it is usually suggested that toxicities are inversely proportional to the size of the NPs [91]. Silver nanoparticles (NPs) are toxic to bacteria, and are currently used in everything from medical devices to sport socks and washing machines to deter microbial growth. Silver is a particularly toxic heavy metal as it interferes with the electron transport chain and binds to DNA [79].
However, the use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome bacteria-nanoparticles interaction. Nanoparticles often have interesting characteristics, including toxicity, that may attract or deter motile bacteria from encountering them. Nanomaterials could potentially act as chemoattractants by creating favorable environments for hydrogenotrophic microorganisms, or could be chemorepellents because of the release of toxic ions [37]. Since a long time, mechanisms of chemotaxis remain unclear because of the complex chemotaxis systems in certain bacteria species.
In this review, we will summarize the current research on nanoparticles and how these one can be applied in the future to fight multidrug resistant
Bacterial chemotaxis is a biased movement towards higher concentrations of life-sustaining nutrients and lower concentrations of toxins. It involves sensing a gradient of chemicals as small as a few molecules [84]. Interestingly, the bacterial movement and under the influence of a chemical gradient, either toward (positive chemotaxis) or away (negative chemotaxis) from the gradient helps bacteria to find optimum conditions for their growth and survival [29]. This is achieved through a variety of signal transduction pathways that most commonly include one-component systems, two-component systems, and chemoreceptor-based signaling cascades [57], also referred to as chemotaxis or chemosensory systems [84].
Chemotaxis in
Furthermore, the chemoeffector repertoire of
For instance, when a toxic compound is present in the environment, bacteria can detect it and swim away [52].
Harrison et al. [28] has also shown that ions of several metals, such as, silver, copper, and gallium, exert bactericidal and antibiofilm activities against
Metal contamination has been linked to birth defects, cancer, skin lesions, mental and physical retardation, learning disabilities, liver and kidney damage and a host of other diseases [75]. Thus, heavy metals pose a critical concern to human health and environmental issues due to their high occurrence as a contaminant, low solubility in biota and the classification of several heavy metals as carcinogenic and mutagenic [17].
Heavy metals are the primary inorganic contaminants, which include cadmium, chromium, copper, lead, mercury, nickel and zinc etc. It was observed that some bacteria could survive and grow even at high metal ion concentrations such as
It quickly became apparent that the effects of heavy metal ions on
It is also interesting to note that the structure dependent metabolic heterogeneity may also explain, in part, the tolerance of bacterial biofilms to metal ions. In
As reported by Wagner-Döbler et al. [85] electron microscopy revealed that a
Another line of research is devoted to nanotechnology, which produced materials of various types at nanoscale level. The continuous emergence of bacterial resistance has challenged the research community to develop novel antibiotic agents. Among the most promising of these novel antibiotic agents are metal NPs, which have shown strong antibacterial activity in an overwhelming number of studies [76]. Nanoparticles (NPs) are wide class of materials that include particulate substances, which have one dimension less than 100 nm at least [40]. These inorganic particles of either simple or complex nature, display unique, physical and chemical properties and represent an increasingly important material in the development of novel nanodevices which can be used in numerous physical, biological, biomedical and pharmaceutical applications [48]. It is also noteworthy that nanoparticles (NPs) show unique and considerably changed chemical, physical, and biological properties compared to bulk of the same chemical composition, due to their high surface-to volume ratio. NPs exhibit size and shape-dependent properties which are of interest for applications ranging from biosensing, catalysts to optics and antimicrobial activity [33]. With an antimicrobial one, nanoparticles are used for their high penetrability into bacterial membranes. They can disrupt biofilm formation, possess multiple antimicrobial mechanisms, and are good carriers of antibiotics [86]. The metallic and antimicrobial agent-loaded nanoparticles have been extensively studied, the nanocomposite films displayed a significant antibacterial activity against
Furthermore, AshaRani et al. [4] reported that AgNPs are being used increasingly in wound dressings, catheters and various households products due to their antimicrobial activity. Antimicrobial agents are extremely vital in textile, medicine, water disinfection and food packaging. Therefore, the antimicrobial characteristics of inorganic NPs add more potency to this important aspect, as compared to organic compounds, which are relatively toxic to the biological systems [26]. On the other hand, understanding these phenomena will allow researchers to explain the application of nanotherapy.
Nowadays, it is known the disadvantage of using nanoparticles and their potential toxicity, but these tiny materials presented a great antimicrobial activity and have been used in a variety of chemical, biological and biomedical applications [34]. NPs have a number of features, which make them favorable as vectors for drugs to combat disease-causing pathogens. These include their enhancement of drug solubility and stability [32]; their ease of synthesis [22] and their modulated release [77] or biocompatibility with target components cells. Slavin et al. [76] reported that the most effective NPs
It is worth noting that the mode of action of NPs is direct contact with the bacterial cell wall, without the need to penetrate the cell. Ma and Lin [50] mentioned that once NPs come into contact with cell surfaces, they may be adsorbed on the cell walls or membranes by multiple forces, and then it is likely that they will enter the cells through various routes. The biophysicochemical interactions at the interfaces between the NPs and cells, in conclusion, mainly include adsorption and internalization.
Thus, NPs need to be in contact with bacterial cells to achieve their antibacterial function
NPs do not present the same mechanisms of action of standard antibiotics but they can exert a multitude of mechanisms (Fig. 1).
Fig. 1
With different size, shape, stiffness and surface charge NPs cross the bacterial membrane and disrupt cell membrane and wall, influencing several pathways. NPs trigger a generation of oxidative stress (ROS) that damage cellular proteins and cell’s basic components (DNA, ribosomes, enzymes), leading to changes in cell membrane permeability, metabolism pathways and biofilm disruption.
Both Gram-positive and negative bacteria have a negatively charged cell wall, a characteristic that is hypothesized to influence the interactions between the cell walls of the bacteria and NPs or ions released from them. The components of the cell membrane produce different adsorption pathways for NPs and Gram-positive and Gram-negative bacteria [43]. Studies performed in Gram-negative bacteria such as
Moreover, Gram-negative bacteria, such as
NPs have emerged as alternative antimicrobial approach to combat biofilms and for treating severe bacterial infections [56]. The antibacterial activity of NPs against multidrug-resistant (MDR) bacteria and biofilms depends on a number of factors, namely, their large surface area in contact with bacteria through the mentioned interactions; on the nanoparticle size and stability; together with the drug concentration [46]. The molecular mechanisms, by which metal-based NPs annihilate MDR bacteria, resulting in disturbance in respiration and inhibition of cellular growth, have been extensively reviewed [15, 18]. Fabrega et al. [19] results suggested that
Furthermore, and in another report, thirty-six metal ions have been investigated to identify antivirulence and antibiofilm metal ions. Zinc ions and ZnO nanoparticles were found to markedly inhibit biofilm formation and the production of pyocyanin,
Another engineered nanoparticle was found to improve the survival rate and the bacterial clearance in a mouse model of
Previous studies have shown that, Zinc ions and ZnO nanoparticles were found to markedly inhibit biofilm formation and the production of pyocyanin,
The interaction of NPs with bacteria generally triggers oxidative stress mechanisms, enzymatic inhibition, protein deactivation and changes in gene expression. Still, the most common antibacterial mechanisms are related to oxidative stress, metal ion release, and non-oxidative mechanisms [86]. As reported by these authors, ROS is a generic term for molecules and reactive intermediates that have strong positive redox potential, and different types of NPs produce different types of ROS by reducing oxygen molecules. Reactive oxygen species (ROS) are natural by products of cellular oxidative metabolism and play important roles in the modulation of cell survival, cell death, differentiation, cell signaling, and inflammation-related factor production [55]. Different NPs may generate distinctive ROS, such as superoxide (O-2) or hydroxyl radical (· OH), hydrogen peroxide (H2O2), and 1[O2]) [86]. Umamaheswari et al. [81] demonstrated that the antibacterial activity of AuNPs against
Under high levels of stress, the levels of ROS can increase significantly and it is hypothesized that their generation is one of the focal NP mechanisms of action that inhibit bacterial growth [61, 45]. Compared with microparticles or their bulk of origin, NPs possess unique physicochemical properties (size, surface area, shape, solubility, and aggregation status) that correlate with their potential to generate ROS [87]. Previous reports illustrated the impact of reactive surfaces of NPs in ROS production [82]. Excessive ROS caused lipid peroxidation, membrane permeability augmentation, and oxidation damage of DNA, RNA, and proteins in bacteria. Bao et al [6] also found that AgNPs could inhibit new DNA synthesis in the cells.
Furthermore, several research reports evidenced the role of oxidative stress in NP-induced antimicrobial activity. Biologically-synthesized AgNPs showed potent antimicrobial activity against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. The significant antimicrobial effect of AgNP is attributed to its potential up-regulation of ROS and reactive nitrogen intermediates that eventually leads to killing of the bacteria [68]. In the same way, nanosilver ions are used as the center of catalytic activity to activate the oxygen in air or water, leading to the production of hydroxyl radicals and reactive oxygen ions, which prevent the proliferation of bacteria or kill them [92]. Furthermore, ROS are beneficial to increasing the gene expression levels of oxidative proteins, which is a key mechanism in bacterial cell apoptosis [90].
These authors reported the significant antimicrobial effect of AgNP, which is attributed to its potential up-regulation of ROS and reactive nitrogen intermediates that eventually leads to killing of the bacteria. Iron oxide NP (IONPs) that coated with the positively charged chitosan possesses special interface that showed significant production of ROS, which is involved in its significant antimicrobial activity against Escherichia coli and Bacillus subtilis [3].
As mentioned above AgNPs are potent inducers of reactive oxygen species. The augmented reactive species levels are known to affect and damage the major bio-molecules, such as nucleic acids and proteins [93]. This nanoparticle-generated oxidative stress, in turn, may also affect the cellular metabolic systems, thereby resulting in increased productivity of certain metabolites [8]. The entry of AgNPs induces ROS that will inhibit ATP production and DNA replication [15]. Feng et al. [21] reported the presence of silver ions and sulfur in the electron-dense granules observed after silver ions treatment in the cytoplasm of bacterial cells suggests an interaction with nucleic acids that probably results in impairment of DNA replication.
Others researchers reported that the plausible mechanism of action of TiO2 NPs against the bacteria could be ROS generation, DNA damage after internalization, peroxidation of membrane phospholipids and inhibition of respiration [38, 80]. Additionally, it has been described that iron oxide NPs can damage macromolecules, including DNA and proteins, through the formation of ROS [44]. Sarwar et al. [73] data demonstrated that nanosized ZnO caused significant oxidative stress to
Another study observed that copper oxide NPs generate ROS that often leads to chromosomal DNA degradation, which seems to highlight a “particle-specific” action rather than resulting from the release of metallic ions [12].
Inhibition of DNA replication and DNA degradation has also been reported with Cu NPs in Chatterjee et al. [13] study. Thus, the potentials of NPs for use as tags of DNA, proteins, microbes, and other cellular molecules make them promising materials for various diagnostic applications [11].
Beside certain toxicities associated with nanoparticles, there has been growing interest in the development of their use in medical applications; they are suitable candidates for the treatment of various bacterial infections. This review provided a proposed hypothesis of the application of metals in another positive way of nanotechnology. However, future studies that utilize nanoparticles need to focus on understanding the bacterial chemotaxis to optimize their functioning in medical applications.