Molecular Mechanisms of Bacterial Resistance to Metal and Metal Oxide Nanoparticles. - Related Documents




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954801.0000Molecular Mechanisms of Bacterial Resistance to Metal and Metal Oxide Nanoparticles. The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. However, until recently, the bacterial resistance mechanisms to the bactericidal action of the nanoparticles had not been investigated. Some of the recently reported resistance mechanisms include electrostatic repulsion, ion efflux pumps, expression of extracellular matrices, and the adaptation of biofilms and mutations. The objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles.201931181755
954910.9999Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review. The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.202437907198
954420.9999Nano-Strategies to Fight Multidrug Resistant Bacteria-"A Battle of the Titans". Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies. Bacteria have developed many ways by which they become resistant to antimicrobials. Among those are enzyme inactivation, decreased cell permeability, target protection, target overproduction, altered target site/enzyme, increased efflux due to over-expression of efflux pumps, among others. Other more complex phenotypes, such as biofilm formation and quorum sensing do not appear as a result of the exposure of bacteria to antibiotics although, it is known that biofilm formation can be induced by antibiotics. These phenotypes are related to tolerance to antibiotics in bacteria. Different strategies, such as the use of nanostructured materials, are being developed to overcome these and other types of resistance. Nanostructured materials can be used to convey antimicrobials, to assist in the delivery of novel drugs or ultimately, possess antimicrobial activity by themselves. Additionally, nanoparticles (e.g., metallic, organic, carbon nanotubes, etc.) may circumvent drug resistance mechanisms in bacteria and, associated with their antimicrobial potential, inhibit biofilm formation or other important processes. Other strategies, including the combined use of plant-based antimicrobials and nanoparticles to overcome toxicity issues, are also being investigated. Coupling nanoparticles and natural-based antimicrobials (or other repurposed compounds) to inhibit the activity of bacterial efflux pumps; formation of biofilms; interference of quorum sensing; and possibly plasmid curing, are just some of the strategies to combat multidrug resistant bacteria. However, the use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome this. In this review, we will summarize the current research on nanoparticles and other nanomaterials and how these are or can be applied in the future to fight multidrug resistant bacteria.201830013539
954030.9999Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents. The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.201122029522
914540.9999A mechanistic perspective on targeting bacterial drug resistance with nanoparticles. Bacterial infections are an important cause of mortality worldwide owing to the prevalence of drug resistant bacteria. Bacteria develop resistance against antimicrobial drugs by several mechanisms such as enzyme inactivation, reduced cell permeability, modifying target site or enzyme, enhanced efflux because of high expression of efflux pumps, biofilm formation or drug-resistance gene expression. New and alternative ways such as nanoparticle (NP) applications are being established to overcome the growing multidrug-resistance in bacteria. NPs have unique antimicrobial characteristics that make them appropriate for medical application to overcome antibiotic resistance. The proposed antibacterial mechanisms of NPs are cell membrane damage, changing cell wall penetration, reactive oxygen species (ROS) production, effect on DNA and proteins, and impact on biofilm formation. The present review mainly focuses on discussing various mechanisms of bacterial drug resistance and the applications of NPs as alternative antibacterial systems. Combination therapy of NPs and antibiotics as a novel approach in medicine towards antimicrobial resistance is also discussed.202133703979
954150.9999The Role of the Hfq Protein in Bacterial Resistance to Antibiotics: A Narrative Review. The antibiotic resistance of pathogenic microorganisms is currently one of most major medical problems, causing a few million deaths every year worldwide due to untreatable bacterial infections. Unfortunately, the prognosis is even worse, as over 8 million deaths associated with antibiotic resistance are expected to occur in 2050 if no new effective antibacterial treatments are discovered. The Hfq protein has been discovered as a bacterial RNA chaperone. However, subsequent studies have indicated that this small protein (composed of 102 amino acid residues in Escherichia coli) has more activities, including binding to DNA and influencing its compaction, interaction with biological membranes, formation of amyloid-like structures, and others. Although Hfq is known to participate in many cellular processes, perhaps surprisingly, only reports from recent years have demonstrated its role in bacterial antibiotic resistance. The aim of this narrative review is to discuss how can Hfq affects antibiotic resistance in bacteria and propose how this knowledge may facilitate developing new therapeutic strategies against pathogenic bacteria. We indicate that the mechanisms by which the Hfq protein modulates the response of bacterial cells to antibiotics are quite different, from the regulation of the expression of genes coding for proteins directly involved in antibiotic transportation or action, through direct effects on membranes, to controlling the replication or transposition of mobile genetic elements bearing antibiotic resistance genes. Therefore, we suggest that Hfq could be considered a potential target for novel antimicrobial compounds. We also discuss difficulties in developing such drugs, but since Hfq appears to be a promising target for drugs that may enhance the efficacy of antibiotics, we propose that works on such potential therapeutics are encouraged.202540005731
913460.9999Mechanism of drug resistance in bacteria: efflux pump modulation for designing of new antibiotic enhancers. Drug resistance has now become a serious concern in the domain of microbial infection. Bacteria are becoming smarter by displaying a variety of mechanisms during drug resistance. It is not only helping bacteria to adapt nicely in adverse environment but it also makes a smart system for better availability of nutritional status for microorganisms. In this domain, pathogenic bacteria are extensively studied and their mechanism for drug resistance is well explored. The common modes in bacterial resistance include degradation of antibiotics by enzymes, antibiotic target modification or inactivation by enzymatic actions, complete replacement of antibiotic targets, quorum sensing (QS) mechanism, and efflux pump-based extrusion of antibiotics. In this review, various mechanisms of drug resistance in bacteria have been highlighted with giving the importance of efflux pumps. This can be explored as a knowledge source for the management of a variety of bacterial infections, related disease and vibrant clue for next-generation drug development.202134431062
954770.9998Confronting antibiotic-resistant pathogens: Distinctive drug delivery potentials of progressive nanoparticles. Antimicrobial resistance arises over time, usually due to genetic modifications. Global observations of high resistance rates to popular antibiotics used to treat common bacterial diseases, such as diarrhea, STIs, sepsis, and urinary tract infections, indicate that our supply of effective antibiotics is running low. The mechanisms of action of several antibiotic groups are covered in this review. Antimicrobials disrupt the development and metabolism of bacteria, leading to their eventual death. However, in recent years, microorganisms become resistant to the drugs. Bacteria encode resistant genes against antibiotics and inhibit the function of antibiotics by reducing the uptake of drugs, modifying the enzyme's active site, synthesizing enzymes to degrade antibiotics, and changing the structure of ribosomal subunits. Additionally, the methods of action of resistant bacteria against different kinds of antibiotics as well as their modes of action are discussed. Besides, the resistant pathogenic bacteria which get the most priority by World Health Organisation (WHO) for synthesizing new drugs, have also been incorporated. To overcome antimicrobial resistance, nanomaterials are used to increase the efficacy of antimicrobial drugs. Metallic, inorganic, and polymer-based nanoparticles once conjugated with antibacterial drugs, exhibit synergistic effects by increasing the efficacy of the drugs by inhibiting bacterial growth. Nanomaterial's toxic properties are proportional to their concentrations. Higher concentration nanomaterials are more toxic to the cells. In this review, the toxic properties of nanomaterials on lung cells, lymph nodes, and neuronal cells are also summarized.202438097117
913580.9998Multidrug Resistance Pumps as a Keystone of Bacterial Resistance. Antibiotic resistance is a global problem of modern medicine. A harbinger of the onset of the postantibiotic era is the complexity and high cost of developing new antibiotics as well as their inefficiency due to the rapidly developing resistance of bacteria. Multidrug resistance (MDR) pumps, involved in the formation of resistance to xenobiotics, the export of toxins, the maintenance of cellular homeostasis, and the formation of biofilms and persistent cells, are the keystone of bacterial protection against antibiotics. MDR pumps are the basis for the nonspecific protection of bacteria, while modification of the drug target, inactivation of the drug, and switching of the target or sequestration of the target is the second specific line of their protection. Thus, the nonspecific protection of bacteria formed by MDR pumps is a barrier that prevents the penetration of antibacterial substances into the cell, which is the main factor determining the resistance of bacteria. Understanding the mechanisms of MDR pumps and a balanced assessment of their contribution to total resistance, as well as to antibiotic sensitivity, will either seriously delay the onset of the postantibiotic era or prevent its onset in the foreseeable future.202236843647
951690.9998Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants. The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics.201829412107
9522100.9998Conjugation Inhibitors and Their Potential Use to Prevent Dissemination of Antibiotic Resistance Genes in Bacteria. Antibiotic resistance has become one of the most challenging problems in health care. Bacteria conjugation is one of the main mechanisms whereby bacteria become resistant to antibiotics. Therefore, the search for specific conjugation inhibitors (COINs) is of interest in the fight against the spread of antibiotic resistances in a variety of laboratory and natural environments. Several compounds, discovered as COINs, are promising candidates in the fight against plasmid dissemination. In this review, we survey the effectiveness and toxicity of the most relevant compounds. Particular emphasis has been placed on unsaturated fatty acid derivatives, as they have been shown to be efficient in preventing plasmid invasiveness in bacterial populations. Biochemical and structural studies have provided insights concerning their potential molecular targets and inhibitory mechanisms. These findings open a new avenue in the search of new and more effective synthetic inhibitors. In this pursuit, the use of structure-based drug design methods will be of great importance for the screening of ligands and binding sites of putative targets.201729255449
9121110.9998The role of efflux pumps ın antıbıotıc resıstance of gram negatıve rods. Antibiotic resistance is an important public health problem today, causing increased morbidity and mortality. Resistance to antibiotics in bacteria can develop by various mechanisms such as a change in the target site of the drug, a change in the outer membrane permeability, enzymatic defusing of the drug and efflux of the antimicrobial compound. Some bacteria have the potential to develop resistance to more than one drug by using several mechanisms together. One of the important resistance mechanisms of bacteria is active efflux pumps (EPs). EPs are pump proteins found in all cell types, located in the cell membrane. They are responsible for the excretion of various intracellular and extracellular substances (antibiotics, etc.) out of the cell. There is much research on various antimicrobials that cause antibiotic resistance in Gram negative rods, but studies on EPs are relatively few. Due to the concern that antibiotics will be insufficient in the treatment of diseases, a good understanding of EPs and the discovery of new EP inhibitors will shed light on the future of humanity. In this review, the structure of bacterial EPs in Gram negative bacteria, the role of EPs in multidrug resistance, the importance of EP inhibitors in the fight against antibiotic resistance and the phenotypic and genotypic detection methods of EPs are discussed.202337060362
9129120.9998Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria. The global increase in multi-drug-resistant bacteria is severely impacting our ability to effectively treat common infections. For Gram-negative bacteria, their intrinsic and acquired resistance mechanisms are heightened by their unique cell wall structure. The cell wall, while being a target of some antibiotics, represents a barrier due to the inability of most antibacterial compounds to traverse and reach their intended target. This means that its composition and resulting mechanisms of resistance must be considered when developing new therapies. Here, we discuss potential antibiotic targets within the most well-characterised resistance mechanisms associated with the cell wall in Gram-negative bacteria, including the outer membrane structure, porins and efflux pumps. We also provide a timely update on the current progress of inhibitor development in these areas. Such compounds could represent new avenues for drug discovery as well as adjuvant therapy to help us overcome antibiotic resistance.202032961699
4286130.9998Disinfectant resistance in bacteria: Mechanisms, spread, and resolution strategies. Disinfectants are widely acknowledged for removing microorganisms from the surface of the objects and transmission media. However, the emergence of disinfectant resistance has become a severe threat to the safety of life and health and the rational allocation of resources due to the reduced disinfectant effectiveness. The horizontal gene transfer (HGT) of disinfectant resistance genes has also expanded the resistant flora, making the situation worse. This review focused on the resistance mechanisms of disinfectant resistant bacteria on biofilms, cell membrane permeability, efflux pumps, degradable enzymes, and disinfectant targets. Efflux can be the fastest and most effective resistance mechanism for bacteria to respond to stress. The qac genes, located on some plasmids which can transmit resistance through conjugative transfer, are the most commonly reported in the study of disinfectant resistance genes. Whether the qac genes can be transferred through transformation or transduction is still unclear. Studying the factors affecting the resistance of bacteria to disinfectants can find breakthrough methods to more adequately deal with the problem of reduced disinfectant effectiveness. It has been confirmed that the interaction of probiotics and bacteria or the addition of 4-oxazolidinone can inhibit the formation of biofilms. Chemicals such as eugenol and indole derivatives can increase bacterial sensitivity by reducing the expression of efflux pumps. The role of these findings in anti-disinfectant resistance has proved invaluable.202133617866
9546140.9998Challenge in the Discovery of New Drugs: Antimicrobial Peptides against WHO-List of Critical and High-Priority Bacteria. Bacterial resistance has intensified in recent years due to the uncontrolled use of conventional drugs, and new bacterial strains with multiple resistance have been reported. This problem may be solved by using antimicrobial peptides (AMPs), which fulfill their bactericidal activity without developing much bacterial resistance. The rapid interaction between AMPs and the bacterial cell membrane means that the bacteria cannot easily develop resistance mechanisms. In addition, various drugs for clinical use have lost their effect as a conventional treatment; however, the synergistic effect of AMPs with these drugs would help to reactivate and enhance antimicrobial activity. Their efficiency against multi-resistant and extensively resistant bacteria has positioned them as promising molecules to replace or improve conventional drugs. In this review, we examined the importance of antimicrobial peptides and their successful activity against critical and high-priority bacteria published in the WHO list.202134064302
4243150.9998Action and resistance mechanisms of antibiotics: A guide for clinicians. Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and "bypass" of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.201729109626
9523160.9998Intrinsic antibiotic resistance: mechanisms, origins, challenges and solutions. The intrinsic antibiotic resistome is a naturally occurring phenomenon that predates antibiotic chemotherapy and is present in all bacterial species. In addition to the intrinsic resistance mediated by the bacterial outer membrane and active efflux, studies have shown that a surprising number of additional genes and genetic loci also contribute to this phenotype. Antibiotic resistance is rife in both the clinic and the environment; novel therapeutic strategies need to be developed in order to prevent a major global clinical threat. The possibility of inhibiting elements comprising the intrinsic resistome in bacterial pathogens offers the promise for repurposing existing antibiotics against intrinsically resistant bacteria.201323499305
9537170.9998Antimicrobial Resistance and Inorganic Nanoparticles. Antibiotics are being less effective, which leads to high mortality in patients with infections and a high cost for the recovery of health, and the projections that are had for the future are not very encouraging which has led to consider antimicrobial resistance as a global health problem and to be the object of study by researchers. Although resistance to antibiotics occurs naturally, its appearance and spread have been increasing rapidly due to the inappropriate use of antibiotics in recent decades. A bacterium becomes resistant due to the transfer of genes encoding antibiotic resistance. Bacteria constantly mutate; therefore, their defense mechanisms mutate, as well. Nanotechnology plays a key role in antimicrobial resistance due to materials modified at the nanometer scale, allowing large numbers of molecules to assemble to have a dynamic interface. These nanomaterials act as carriers, and their design is mainly focused on introducing the temporal and spatial release of the payload of antibiotics. In addition, they generate new antimicrobial modalities for the bacteria, which are not capable of protecting themselves. So, nanoparticles are an adjunct mechanism to improve drug potency by reducing overall antibiotic exposure. These nanostructures can overcome cell barriers and deliver antibiotics to the cytoplasm to inhibit bacteria. This work aims to give a general vision between the antibiotics, the nanoparticles used as carriers, bacteria resistance, and the possible mechanisms that occur between them.202134884695
9138180.9998Carbon-Based Nanomaterials Alter the Behavior and Gene Expression Patterns of Bacteria. One of the most dangerous characteristics of bacteria is their propensity to form biofilms and their resistance to the drugs used in clinical practice today. The total number of genes that can be categorized as virulence genes ranges from a few hundred to more than a thousand. The bacteria employ a variety of mechanisms to regulate the expression of these genes in a coordinated manner during infection. The search for new agents with anti-virulence capacity is therefore crucial. Nanotechnology provides safe platforms for targeted therapies to combat a broad spectrum of microbial infections. As a new class of innovative materials, carbon-based nanomaterials (CBNs), which include carbon dots, carbon nanotubes, graphene, and fullerenes can have strong antibacterial activity. Exposure to CBNs has been shown to affect bacterial gene expression patterns. This study investigated the effect of CBNs on the repression of specific genes related to bacterial virulence/pathogenicity.202539895035
9127190.9998Antimicrobial Peptides: Virulence and Resistance Modulation in Gram-Negative Bacteria. Growing resistance to antibiotics is one of the biggest threats to human health. One of the possibilities to overcome this resistance is to use and develop alternative molecules such as antimicrobial peptides (AMPs). However, an increasing number of studies have shown that bacterial resistance to AMPs does exist. Since AMPs are immunity molecules, it is important to ensure that their potential therapeutic use is not harmful in the long term. Recently, several studies have focused on the adaptation of Gram-negative bacteria to subinhibitory concentrations of AMPs. Such concentrations are commonly found in vivo and in the environment. It is therefore necessary to understand how bacteria detect and respond to low concentrations of AMPs. This review focuses on recent findings regarding the impact of subinhibitory concentrations of AMPs on the modulation of virulence and resistance in Gram-negative bacteria.202032092866