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843600.9844NIR-Activated Hydrogel with Dual-Enhanced Antibiotic Effectiveness for Thorough Elimination of Antibiotic-Resistant Bacteria. Antibiotic resistance has become a critical health crisis globally. Traditional strategies using antibiotics can lead to drug-resistance, while inorganic antimicrobial agents can cause severe systemic toxicity. Here, we have developed a dual-antibiotic hydrogel delivery system (PDA-Ag@Levo/CMCS), which can achieve controlled release of clinical antibiotics levofloxacin (Levo) and classic nanoscale antibiotic silver nanoparticles (AgNPs), effectively eliminating drug-resistant P. aeruginosa. Benefiting from the photothermal (PTT) effect of polydopamine (PDA), the local high temperature generated by PDA-Ag@Levo/CMCS can quickly kill bacteria through continuous and responsive release of dual-antibiotics to restore sensitivity to ineffective antibiotics. Moreover, AgNPs could significantly improve the efficiency of traditional antibiotics by disrupting bacterial membranes and reducing their toxicity to healthy tissues. A clever combination of PTT and drug-combination therapy can effectively eliminate biofilms and drug-resistant bacteria. Mechanism studies have shown that PDA-Ag@Levo might eliminate drug-resistant P. aeruginosa by disrupting biofilm formation and protein synthesis, and inhibit the resistance mutation of P. aeruginosa by promoting the expression of related genes, such as rpoS, dinB, and mutS. Collectively, the synergistic effect of this dual-antibiotic hydrogel combined with PTT provides a creative strategy for eliminating drug-resistant bacteria in chronic infection wounds.202539760335
914410.9839Metal nanoparticles: understanding the mechanisms behind antibacterial activity. 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.201728974225
861420.9836Polystyrene nanoparticles induce biofilm formation in Pseudomonas aeruginosa. In recent years, micro/nanoplastics have garnered widespread attention due to their ecological risks. In this study, we investigated the effects of polystyrene nanoparticles (PS-NPs) of different sizes on the growth and biofilm formation of Pseudomonas aeruginosa PAO1. The results demonstrated that exposure to certain concentrations of PS-NPs significantly promoted bacterial biofilm formation. Meanwhile, we comprehensively revealed its mechanism whereby PS-NPs induced oxidative stress and altered bacterial membrane permeability by contacting or penetrating bacterial membranes. To counteract the stimulation by PS-NPs and reduce their toxicity, bacteria enhanced biofilm formation by upregulating the expression of biofilm-related genes, increasing EPS and virulence factors secretion, and enhancing bacterial motility through the participation of the quorum sensing (QS) system. Additionally, we also found that exposure to PS-NPs enhanced bacterial antibiotic resistance, posing a challenge to antimicrobial therapy. Our study reveals the toxic effects of nanoplastics and the defense mechanisms of bacteria, which has important implications for the risk assessment and management of environmental nanoplastics.202438442601
916030.9834Interference in Bacterial Quorum Sensing: A Biopharmaceutical Perspective. Numerous bacteria utilize molecular communication systems referred to as quorum sensing (QS) to synchronize the expression of certain genes regulating, among other aspects, the expression of virulence factors and the synthesis of biofilm. To achieve this process, bacteria use signaling molecules, known as autoinducers (AIs), as chemical messengers to share information. Naturally occurring strategies that interfere with bacterial signaling have been extensively studied in recent years, examining their potential to control bacteria. To interfere with QS, bacteria use quorum sensing inhibitors (QSIs) to block the action of AIs and quorum quenching (QQ) enzymes to degrade signaling molecules. Recent studies have shown that these strategies are promising routes to decrease bacterial pathogenicity and decrease biofilms, potentially enhancing bacterial susceptibility to antimicrobial agents including antibiotics and bacteriophages. The efficacy of QSIs and QQ enzymes has been demonstrated in various animal models and are now considered in the development of new medical devices against bacterial infections, including dressings, and catheters for enlarging the therapeutic arsenal against bacteria.201829563876
644240.9833A systematic review of antibiotic resistance driven by metal-based nanoparticles: Mechanisms and a call for risk mitigation. Elevations in antibiotic resistance genes (ARGs) are due not only to the antibiotic burden, but also to numerous environmental pressures (e.g., pesticides, metal ions, or psychotropic pharmaceuticals), which have led to an international public health emergency. Metal-based nanoparticles (MNPs) poison bacteria while propelling nanoresistance at ambient or sub-lethal concentrations, acting as a wide spectrum germicidal agent. Awareness of MNPs driven antibiotic resistance has created a surge of investigation into the molecule mechanisms of evolving and spreading environmental antibiotic resistome. Co-occurrence of MNPs resistance and antibiotic resistance emerge in environmental pathogens and benign microbes may entail a crucial outcome for human health. In this review we expound on the systematic mechanism of ARGs proliferation under the stress of MNPs, including reactive oxygen species (ROS) induced mutation, horizontal gene transfer (HGT) relevant genes regulation, nano-property, quorum sensing, and biofilm formation and highlighting on the momentous contribution of nanoparticle released ion. As antibiotic resistance pattern alteration is closely knit with the mediate activation of nanoparticle in water, soil, manure, or sludge habitats, we have proposed a virulence and evolution based antibiotic resistance risk assessment strategy for MNP contaminated areas and discussed practicable approaches that call for risk management in critical environmental compartments.202438220012
816050.9833Quorum Sensing in Gram-Negative Bacteria: Strategies to Overcome Antibiotic Resistance in Ocular Infections. Truly miraculous medications and antibiotics have helped save untold millions of lives. Antibiotic resistance, however, is a significant issue related to health that jeopardizes the effectiveness of antibiotics and could harm everyone's health. Bacteria, not humans or animals, become antibiotic-resistant. Bacteria use quorum-sensing communication routes to manage an assortment of physiological exercises. Quorum sensing is significant for appropriate biofilm development. Antibiotic resistance occurs when bacteria establish a biofilm on a surface, shielding them from the effects of infection-fighting drugs. Acylated homoserine lactones are used as autoinducers by gram-negative microscopic organisms to impart. However, antibiotic resistance among ocular pathogens is increasing worldwide. Bacteria are a significant contributor to ocular infections around the world. Gram-negative microscopic organisms are dangerous to ophthalmic tissues. This review highlights the use of elective drug targets and treatments, for example, combinational treatment, to vanquish antibiotic-resistant bacteria. Also, it briefly portrays anti-biotic resistance brought about by gram-negative bacteria and approaches to overcome resistance with the help of quorum sensing inhibitors and nanotechnology as a promising medication conveyance approach to give insurance of anti-microbials and improve pathways for the administration of inhibitors of quorum sensing with a blend of anti-microbials to explicit target destinations and penetration through biofilms for treatment of ocular infections. It centres on the methodologies to sidestep the confinements of ocular anti-biotic delivery with new visual innovation.202437497706
828360.9833Stress responses as determinants of antimicrobial resistance in Gram-negative bacteria. Bacteria encounter a myriad of potentially growth-compromising conditions in nature and in hosts of pathogenic bacteria. These 'stresses' typically elicit protective and/or adaptive responses that serve to enhance bacterial survivability. Because they impact upon many of the same cellular components and processes that are targeted by antimicrobials, adaptive stress responses can influence antimicrobial susceptibility. In targeting and interfering with key cellular processes, antimicrobials themselves are 'stressors' to which protective stress responses have also evolved. Cellular responses to nutrient limitation (nutrient stress), oxidative and nitrosative stress, cell envelope damage (envelope stress), antimicrobial exposure and other growth-compromising stresses, have all been linked to the development of antimicrobial resistance in Gram-negative bacteria - resulting from the stimulation of protective changes to cell physiology, activation of resistance mechanisms, promotion of resistant lifestyles (biofilms), and induction of resistance mutations.201222424589
819070.9833Identification of Quorum-Sensing Inhibitors Disrupting Signaling between Rgg and Short Hydrophobic Peptides in Streptococci. Bacteria coordinate a variety of social behaviors, important for both environmental and pathogenic bacteria, through a process of intercellular chemical signaling known as quorum sensing (QS). As microbial resistance to antibiotics grows more common, a critical need has emerged to develop novel anti-infective therapies, such as an ability to attenuate bacterial pathogens by means of QS interference. Rgg quorum-sensing pathways, widespread in the phylum Firmicutes, employ cytoplasmic pheromone receptors (Rgg transcription factors) that directly bind and elicit gene expression responses to imported peptide signals. In the human-restricted pathogen Streptococcus pyogenes, the Rgg2/Rgg3 regulatory circuit controls biofilm development in response to the short hydrophobic peptides SHP2 and SHP3. Using Rgg-SHP as a model receptor-ligand target, we sought to identify chemical compounds that could specifically inhibit Rgg quorum-sensing circuits. Individual compounds from a diverse library of known drugs and drug-like molecules were screened for their ability to disrupt complexes of Rgg and FITC (fluorescein isothiocyanate)-conjugated SHP using a fluorescence polarization (FP) assay. The best hits were found to bind Rgg3 in vitro with submicromolar affinities, to specifically abolish transcription of Rgg2/3-controlled genes, and to prevent biofilm development in S. pyogenes without affecting bacterial growth. Furthermore, the top hit, cyclosporine A, as well as its nonimmunosuppressive analog, valspodar, inhibited Rgg-SHP pathways in multiple species of Streptococcus. The Rgg-FITC-peptide-based screen provides a platform to identify inhibitors specific for each Rgg type. Discovery of Rgg inhibitors constitutes a step toward the goal of manipulating bacterial behavior for purposes of improving health. IMPORTANCE: The global emergence of antibiotic-resistant bacterial infections necessitates discovery not only of new antimicrobials but also of novel drug targets. Since antibiotics restrict microbial growth, strong selective pressures to develop resistance emerge quickly in bacteria. A new strategy to fight microbial infections has been proposed, namely, development of therapies that decrease pathogenicity of invading organisms while not directly inhibiting their growth, thus decreasing selective pressure to establish resistance. One possible means to this goal is to interfere with chemical communication networks used by bacteria to coordinate group behaviors, which can include the synchronized expression of genes that lead to disease. In this study, we identified chemical compounds that disrupt communication pathways regulated by Rgg proteins in species of Streptococcus. Treatment of cultures of S. pyogenes with the inhibitors diminished the development of biofilms, demonstrating an ability to control bacterial behavior with chemicals that do not inhibit growth.201525968646
855380.9832Unveiling the power of nanotechnology: a novel approach to eliminating antibiotic-resistant bacteria and genes from municipal effluent. The increasing global population and declining freshwater resources have heightened the urgency of ensuring safe and accessible water supplies.Query The persistence of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in municipal effluents poses a significant public health threat, exacerbated by the widespread use of antibiotics and the inadequate removal of contaminants in wastewater treatment facilities. Conventional treatment methods often fail to eliminate these emerging pollutants, facilitating their entry into agricultural systems and natural water bodies, thereby accelerating the spread of antimicrobial resistance. To address these challenges, interdisciplinary strategies in water treatment are essential. Nanotechnology has emerged as a promising approach due to its unique physicochemical properties, biocompatibility, and high efficiency in detecting and removing biological and chemical contaminants. Various nanomaterials, including graphene-based structures, Carbon nanotubes (CNTs), noble metal nanoparticles (gold (Au) and silver (Ag)), silicon and chitosan-based nanomaterials, as well as titanium and Zinc oxide (ZnO) nanomaterials, demonstrate potent antimicrobial effects. Moreover, nanosensors and photocatalysts utilizing these nanomaterials enable precise detection and effective degradation of ARB and ARGs in wastewater. This review examines the mechanisms by which nanotechnology-based materials can mitigate the risks associated with antibiotic resistance in urban effluents, focusing on their applications in pathogen detection, pollutant removal, and wastewater treatment. By integrating nanotechnology into existing treatment frameworks, we can significantly enhance the efficiency of water purification processes, ultimately contributing to global water security and the protection of public health.202540512401
861690.9832Mechanisms of inhibition and recovery under multi-antibiotic stress in anammox: A critical review. With the escalating global concern for emerging pollutants, particularly antibiotics, microplastics, and nanomaterials, the potential disruption they pose to critical environmental processes like anaerobic ammonia oxidation (anammox) has become a pressing issue. The anammox process, which plays a crucial role in nitrogen removal from wastewater, is particularly sensitive to external pollutants. This paper endeavors to address this knowledge gap by providing a comprehensive overview of the inhibition mechanisms of multi-antibiotic on anaerobic ammonia-oxidizing bacteria, along with insights into their recovery processes. The paper dives deeply into the various ways antibiotics interact with anammox bacteria, focusing specifically on their interference with the bacteria's extracellular polymers (EPS) - crucial components that maintain the structural integrity and functionality of the cells. Additionally, it explores how anammox bacteria utilize quorum sensing (QS) mechanisms to regulate their community structure and respond to antibiotic stress. Moreover, the paper summarizes effective removal methods for these antibiotics from wastewater systems, which is crucial for mitigating their inhibitory effects on anammox bacteria. Finally, the paper offers valuable insights into how anammox communities can recuperate from multi-antibiotic stress. This includes strategies for reintroducing healthy bacteria, optimizing operational conditions, and using bioaugmentation techniques to enhance the resilience of anammox communities. In summary, this paper not only enriches our understanding of the complex interactions between antibiotics and anammox bacteria but also provides theoretical and practical guidance for the treatment of antibiotic pollution in sewage, ensuring the sustainability and effectiveness of wastewater treatment processes.202439366232
9168100.9831Novel approaches to bacterial infection therapy by interfering with bacteria-to-bacteria signaling. The growing challenge of antimicrobial resistance and the paucity of novel antibiotics underscore the importance of developing novel therapeutics. Bacterial cell-to-cell signaling constitutes a novel drug target. Quorum sensing (QS) is a cell-to-cell signaling mechanism that refers to the ability of bacteria to respond to chemical hormone-like molecules called autoinducers. QS is responsible for controlling a plethora of virulence genes in several bacterial pathogens. Antagonists to autoinducers will intercept bacterial intercellular communication, hindering their ability to act in a coordinated manner to express virulence traits. Moreover, since QS is not involved directly in essential processes, such as bacterial growth, one can reason that inhibition of QS will not yield a selective pressure for the development of resistance.200717402841
9161110.9831In Silico Evaluation of the Impacts of Quorum Sensing Inhibition (QSI) on Strain Competition and Development of QSI Resistance. As understanding of bacterial regulatory systems and pathogenesis continues to increase, QSI has been a major focus of research. However, recent studies have shown that mechanisms of resistance to quorum sensing (QS) inhibitors (QSIs) exist, calling into question their clinical value. We propose a computational framework that considers bacteria genotypes relative to QS genes and QS-regulated products including private, quasi-public, and public goods according to their impacts on bacterial fitness. Our results show (1) QSI resistance spreads when QS positively regulates the expression of private or quasi-public goods. (2) Resistance to drugs targeting secreted compounds downstream of QS for a mix of private, public, and quasi-public goods also spreads. (3) Changing the micro-environment during treatment with QSIs may decrease the spread of resistance. At fundamental-level, our simulation framework allows us to directly quantify cell-cell interactions and biofilm dynamics. Practically, the model provides a valuable tool for the study of QSI-based therapies, and the simulations reveal experimental paths that may guide QSI-based therapies in a manner that avoids or decreases the spread of QSI resistance.201627734907
8599120.9831Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation. Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyi ADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilis and mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects.202234465899
8163130.9831Green materials science and engineering reduces biofouling: approaches for medical and membrane-based technologies. Numerous engineered and natural environments suffer deleterious effects from biofouling and/or biofilm formation. For instance, bacterial contamination on biomedical devices pose serious health concerns. In membrane-based technologies, such as desalination and wastewater reuse, biofouling decreases membrane lifetime, and increases the energy required to produce clean water. Traditionally, approaches have combatted bacteria using bactericidal agents. However, due to globalization, a decline in antibiotic discovery, and the widespread resistance of microbes to many commercial antibiotics and metallic nanoparticles, new materials, and approaches to reduce biofilm formation are needed. In this mini-review, we cover the recent strategies that have been explored to combat microbial contamination without exerting evolutionary pressure on microorganisms. Renewable feedstocks, relying on structure-property relationships, bioinspired/nature-derived compounds, and green processing methods are discussed. Greener strategies that mitigate biofouling hold great potential to positively impact human health and safety.201525852659
9146140.9831Emergence of microbial resistance against nanoparticles: Mechanisms and strategies. Antimicrobial nanoparticles have gained the status of a new generation of drugs that can kill bacterial pathogens by multiple means; however, nanoparticle resistance acquired by some bacterial pathogens has evoked a cause of concern. Several reports suggested that bacteria can develop nanoparticles, specifically metal nanoparticle resistance, by mechanisms: nanoparticle transformation-induced oxidative stress, membrane alterations, reversible adaptive resistance, irreversible modifications to cell division, and a change in bacterial motility and resistance. Surface properties, concentration and aggregation of nanoparticles, biofilm forming and metal exclusion capacity, and R plasmid and flagellin synthesis by bacteria are crucial factors in the development of nanoparticle resistance in bacteria. Studies reported the resistance reversal by modifying the surface corona of nanoparticles or inhibiting flagellin production by bacterial pathogens. Furthermore, strict regulation regarding the use and disposal of nano-waste across the globe, the firm knowledge of microbe-nanoparticle interaction, and the regulated disposal of nanoparticles in soil and water is required to prevent microbes from developing nanoparticle resistance.202336778867
8435150.9830Antimicrobial Zeolitic Imidazolate Frameworks with Dual Mechanisms of Action. The horizontal transfer of drug-resistant genes and the formation of biofilm barriers have threatened the therapeutic efficacy of conventional antibiotic drugs. Development of non-antibiotic agents with high delivery efficiency through bacterial biofilms is urgently required. A pyrithione (PT)-loading zeolitic imidazolate framework (ZIF-8@PT) is synthesized to destroy biofilms and improve the sensitivity of bacteria to PT. ZIF-8@PT can target and destroy the biofilm as well as the cell membrane, promoting the intracellular delivery of PT and possibly its interaction with SmpB, a protein that could regulate the drug resistance of bacteria. ZIF-8@PT effectively suppresses abdominal infections induced by multiresistant Aeromonas veronii C4 in rodent models without systemic toxicity. ZIF-8@PT promises wide applications in treating infections caused by multidrug-resistant bacteria through a dual mechanism of action.202336815744
8176160.9830Overcoming Multidrug Resistance in Bacteria Through Antibiotics Delivery in Surface-Engineered Nano-Cargos: Recent Developments for Future Nano-Antibiotics. In the recent few decades, the increase in multidrug-resistant (MDR) bacteria has reached an alarming rate and caused serious health problems. The incidence of infections due to MDR bacteria has been accompanied by morbidity and mortality; therefore, tackling bacterial resistance has become an urgent and unmet challenge to be properly addressed. The field of nanomedicine has the potential to design and develop efficient antimicrobials for MDR bacteria using its innovative and alternative approaches. The uniquely constructed nano-sized antimicrobials have a predominance over traditional antibiotics because their small size helps them in better interaction with bacterial cells. Moreover, surface engineering of nanocarriers offers significant advantages of targeting and modulating various resistance mechanisms, thus owe superior qualities for overcoming bacterial resistance. This review covers different mechanisms of antibiotic resistance, application of nanocarrier systems in drug delivery, functionalization of nanocarriers, application of functionalized nanocarriers for overcoming bacterial resistance, possible limitations of nanocarrier-based approach for antibacterial delivery, and future of surface-functionalized antimicrobial delivery systems.202134307323
9177170.9830Multitarget Approaches against Multiresistant Superbugs. Despite efforts to develop new antibiotics, antibacterial resistance still develops too fast for drug discovery to keep pace. Often, resistance against a new drug develops even before it reaches the market. This continued resistance crisis has demonstrated that resistance to antibiotics with single protein targets develops too rapidly to be sustainable. Most successful long-established antibiotics target more than one molecule or possess targets, which are encoded by multiple genes. This realization has motivated a change in antibiotic development toward drug candidates with multiple targets. Some mechanisms of action presuppose multiple targets or at least multiple effects, such as targeting the cytoplasmic membrane or the carrier molecule bactoprenol phosphate and are therefore particularly promising. Moreover, combination therapy approaches are being developed to break antibiotic resistance or to sensitize bacteria to antibiotic action. In this Review, we provide an overview of antibacterial multitarget approaches and the mechanisms behind them.202032156116
8554180.9830Nanomaterial-Enhanced Hybrid Disinfection: A Solution to Combat Multidrug-Resistant Bacteria and Antibiotic Resistance Genes in Wastewater. This review explores the potential of nanomaterial-enhanced hybrid disinfection methods as effective strategies for addressing the growing challenge of multidrug-resistant (MDR) bacteria and antibiotic resistance genes (ARGs) in wastewater treatment. By integrating hybrid nanocomposites and nanomaterials, natural biocides such as terpenes, and ultrasonication, this approach significantly enhances disinfection efficiency compared to conventional methods. The review highlights the mechanisms through which hybrid nanocomposites and nanomaterials generate reactive oxygen species (ROS) under blue LED irradiation, effectively disrupting MDR bacteria while improving the efficacy of natural biocides through synergistic interactions. Additionally, the review examines critical operational parameters-such as light intensity, catalyst dosage, and ultrasonication power-that optimize treatment outcomes and ensure the reusability of hybrid nanocomposites and other nanomaterials without significant loss of photocatalytic activity. Furthermore, this hybrid method shows promise in degrading ARGs, thereby addressing both microbial and genetic pollution. Overall, this review underscores the need for innovative wastewater treatment solutions that are efficient, sustainable, and scalable, contributing to the global fight against antimicrobial resistance.202439591087
9145190.9829A 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