UNCONVENTIONAL - Word Related Documents




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815800.9603Nanobioconjugates: Weapons against Antibacterial Resistance. The increase in drug resistance in pathogenic bacteria is emerging as a global threat as we swiftly edge toward the postantibiotic era. Nanobioconjugates have gained tremendous attention to treat multidrug-resistant (MDR) bacteria and biofilms due to their tunable physicochemical properties, drug targeting ability, enhanced uptake, and alternate mechanisms of drug action. In this review, we highlight the recent advances made in the use of nanobioconjugates to combat antibacterial resistance and provide crucial insights for designing nanomaterials that can serve as antibacterial agents for nanotherapeutics, nanocargos for targeted antibiotic delivery, or both. Also discussed are different strategies for treating robust biofilms formed by bacteria.202035019602
816210.9591Nanotechnology for Targeted Detection and Removal of Bacteria: Opportunities and Challenges. The emergence of nanotechnology has created unprecedented hopes for addressing several unmet industrial and clinical issues, including the growing threat so-termed "antibiotic resistance" in medicine. Over the last decade, nanotechnologies have demonstrated promising applications in the identification, discrimination, and removal of a wide range of pathogens. Here, recent insights into the field of bacterial nanotechnology are examined that can substantially improve the fundamental understanding of nanoparticle and bacteria interactions. A wide range of developed nanotechnology-based approaches for bacterial detection and removal together with biofilm eradication are summarized. The challenging effects of nanotechnologies on beneficial bacteria in the human body and environment and the mechanisms of bacterial resistance to nanotherapeutics are also reviewed.202134558234
817620.9584Overcoming 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
917330.9576Bacterial defences: mechanisms, evolution and antimicrobial resistance. Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution.202337095190
917240.9575These Are the Genes You're Looking For: Finding Host Resistance Genes. Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host-pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics contributes to host resistance or susceptibility to bacterial infection. Here we discuss current trends in defining host-bacterial interactions at the genome-wide level, including screens that harness CRISPR/Cas9 genome editing, natural genetic variation, proteomics, and transcriptomics. We report on the merits, limitations, and findings of these innovative screens and discuss their complementary nature. Finally, we speculate on future innovation as we continue to progress through the postgenomic era and towards deeper mechanistic insight and clinical applications.202133004258
815950.9574Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications. The overuse of antibiotics has led to the emergence of a large number of antibiotic-resistant genes in bacteria, and increasing evidence indicates that a fungicide with an antibacterial mechanism different from that of antibiotics is needed. Quaternary ammonium salts (QASs) are a biparental substance with good antibacterial properties that kills bacteria through simple electrostatic adsorption and insertion into cell membranes/altering of cell membrane permeability. Therefore, the probability of bacteria developing drug resistance is greatly reduced. In this review, we focus on the synthesis and application of single-chain QASs, double-chain QASs, heterocyclic QASs, and gemini QASs (GQASs). Some possible structure-function relationships of QASs are also summarized. As such, we hope this review will provide insight for researchers to explore more applications of QASs in the field of antimicrobials with the aim of developing systems for clinical applications.202336748912
816360.9573Green 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
665570.9572Futuristic Non-antibiotic Therapies to Combat Antibiotic Resistance: A Review. The looming problem of resistance to antibiotics in microorganisms is a global health concern. The drug-resistant microorganisms originating from anthropogenic sources and commercial livestock farming have posed serious environmental and health challenges. Antibiotic-resistant genes constituting the environmental "resistome" get transferred to human and veterinary pathogens. Hence, deciphering the origin, mechanism and extreme of transfer of these genetic factors into pathogens is extremely important to develop not only the therapeutic interventions to curtail the infections, but also the strategies to avert the menace of microbial drug-resistance. Clinicians, researchers and policymakers should jointly come up to develop the strategies to prevent superfluous exposure of pathogens to antibiotics in non-clinical settings. This article highlights the present scenario of increasing antimicrobial-resistance in pathogenic bacteria and the clinical importance of unconventional or non-antibiotic therapies to thwart the infectious pathogenic microorganisms.202133574807
816180.9571Integrative strategies against multidrug-resistant bacteria: Synthesizing novel antimicrobial frontiers for global health. Concerningly, multidrug-resistant bacteria have emerged as a prime worldwide trouble, obstructing the treatment of infectious diseases and causing doubts about the therapeutic accidentalness of presently existing drugs. Novel antimicrobial interventions deserve development as conventional antibiotics are incapable of keeping pace with bacteria evolution. Various promising approaches to combat MDR infections are discussed in this review. Antimicrobial peptides are examined for their broad-spectrum efficacy and reduced ability to develop resistance, while phage therapy may be used under extreme situations when antibiotics fail. In addition, the possibility of CRISPR-Cas systems for specifically targeting and eradicating resistance genes from bacterial populations will be explored. Nanotechnology has opened up the route to improve the delivery system of the drug itself, increasing the efficacy and specificity of antimicrobial action while protecting its host. Discovering potential antimicrobial agents is an exciting prospect through developments in synthetic biology and the rediscovery of natural product-based medicines. Moreover, host-directed therapies are now becoming popular as an adjunct to the main strategies of therapeutics without specifically targeting pathogens. Although these developments appear impressive, questions about production scaling, regulatory approvals, safety, and efficacy for clinical employment still loom large. Thus, tackling the MDR burden requires a multi-pronged plan, integrating newer treatment modalities with existing antibiotic regimens, enforcing robust stewardship initiatives, and effecting policy changes at the global level. The international health community can gird itself against the growing menace of antibiotic resistance if collaboration between interdisciplinary bodies and sustained research endeavours is encouraged. In this study, we evaluate the synergistic potential of combining various medicines in addition to summarizing recent advancements. To rethink antimicrobial stewardship in the future, we provide a multi-tiered paradigm that combines pathogen-focused and host-directed strategies.202540914328
815790.9570Autologous DNA mobilization and multiplication expedite natural products discovery from bacteria. The transmission of antibiotic-resistance genes, comprising mobilization and relocation events, orchestrates the dissemination of antimicrobial resistance. Inspired by this evolutionarily successful paradigm, we developed ACTIMOT, a CRISPR-Cas9-based approach to unlock the vast chemical diversity concealed within bacterial genomes. ACTIMOT enables the efficient mobilization and relocation of large DNA fragments from the chromosome to replicative plasmids within the same bacterial cell. ACTIMOT circumvents the limitations of traditional molecular cloning methods involving handling and replicating large pieces of genomic DNA. Using ACTIMOT, we mobilized and activated four cryptic biosynthetic gene clusters from Streptomyces, leading to the discovery of 39 compounds across four distinct classes. This work highlights the potential of ACTIMOT for accelerating the exploration of biosynthetic pathways and the discovery of natural products.202439666857
8177100.9569Antibiotic action and resistance: updated review of mechanisms, spread, influencing factors, and alternative approaches for combating resistance. Antibiotics represent a frequently employed therapeutic modality for the management of bacterial infections across diverse domains, including human health, agriculture, livestock breeding, and fish farming. The efficacy of antibiotics relies on four distinct mechanisms of action, which are discussed in detail in this review, along with accompanying diagrammatic illustrations. Despite their effectiveness, antibiotic resistance has emerged as a significant challenge to treating bacterial infections. Bacteria have developed defense mechanisms against antibiotics, rendering them ineffective. This review delves into the specific mechanisms that bacteria have developed to resist antibiotics, with the help of diagrammatic illustrations. Antibiotic resistance can spread among bacteria through various routes, resulting in previously susceptible bacteria becoming antibiotic-resistant. Multiple factors contribute to the worsening crisis of antibiotic resistance, including human misuse of antibiotics. This review also emphasizes alternative solutions proposed to mitigate the exacerbation of antibiotic resistance.202338283841
9174110.9569Developing Phage Therapy That Overcomes the Evolution of Bacterial Resistance. The global rise of antibiotic resistance in bacterial pathogens and the waning efficacy of antibiotics urge consideration of alternative antimicrobial strategies. Phage therapy is a classic approach where bacteriophages (bacteria-specific viruses) are used against bacterial infections, with many recent successes in personalized medicine treatment of intractable infections. However, a perpetual challenge for developing generalized phage therapy is the expectation that viruses will exert selection for target bacteria to deploy defenses against virus attack, causing evolution of phage resistance during patient treatment. Here we review the two main complementary strategies for mitigating bacterial resistance in phage therapy: minimizing the ability for bacterial populations to evolve phage resistance and driving (steering) evolution of phage-resistant bacteria toward clinically favorable outcomes. We discuss future research directions that might further address the phage-resistance problem, to foster widespread development and deployment of therapeutic phage strategies that outsmart evolved bacterial resistance in clinical settings.202337268007
8171120.9568Advancements in CRISPR-Cas-based strategies for combating antimicrobial resistance. Multidrug resistance (MDR) in bacteria presents a significant global health threat, driven by the widespread dissemination of antibiotic-resistant genes (ARGs). The CRISPR-Cas system, known for its precision and adaptability, holds promise as a tool to combat antimicrobial resistance (AMR). Although previous studies have explored the use of CRISPR-Cas to target bacterial genomes or plasmids harboring resistance genes, the application of CRISPR-Cas-based antimicrobial therapies is still in its early stages. Challenges such as low efficiency and difficulties in delivering CRISPR to bacterial cells remain. This review provides an overview of the CRISPR-Cas system, highlights recent advancements in CRISPR-Cas-based antimicrobials and delivery strategies for combating AMR. The review also discusses potential challenges for the future development of CRISPR-Cas-based antimicrobials. Addressing these challenges would enable CRISPR therapies to become a practical solution for treating AMR infections in the future.202540440869
8165130.9567Exploring the antibiotic potential of cultured 'unculturable' bacteria. In response to the severe global antibiotic resistance crisis, this forum delves into 'unculturable' bacteria, believed to be a promising source of novel antibiotics. We propose remarkable drug discovery strategies that leverage these bacteria's diversity, aspiring to transform resistance management. The urgent call for new antibiotics accentuates the essentiality of further research.202438102034
9156140.9567Resistance to quorum-quenching compounds. Bacteria have the remarkable ability to communicate as a group in what has become known as quorum sensing (QS), and this trait has been associated with important bacterial phenotypes, such as virulence and biofilm formation. Bacteria also have an incredible ability to evolve resistance to all known antimicrobials. Hence, although inhibition of QS has been hailed as a means to reduce virulence in a manner that is impervious to bacterial resistance mechanisms, this approach is unlikely to be a panacea. Here we review the evidence that bacteria can evolve resistance to quorum-quenching compounds.201324014536
8178150.9566Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions. Antimicrobial resistance is a global health threat. Misuse and overuse of antimicrobials are the main drivers in developing drug-resistant bacteria. The emergence of the rapid global spread of multi-resistant bacteria requires urgent multisectoral action to generate novel treatment alternatives. Combination therapy offers the potential to exploit synergistic effects for enhanced antibacterial efficacy of drugs. Understanding the complex dynamics and kinetics of drug interactions in combination therapy is crucial. Therefore, this review outlines the current advances in antibiotic resistance's evolutionary and genetic dynamics in combination therapies-exposed bacteria. Moreover, we also discussed four pivotal future research areas to comprehend better the development of antibiotic resistance in bacteria treated with combination strategies.202438510041
9578160.9566Type III secretion systems in symbiotic adaptation of pathogenic and non-pathogenic bacteria. The emergence of multi-drug resistance and bacteria with increased virulence is a familiar refrain to the contemporary microbiologist. Although intense research over the past decade has ascribed much molecular detail to these processes, more esoteric questions remain: for example, why are some bacteria evolving increased virulence towards humans, what are the genes underpinning this virulence potential and what are the selective pressures that favor these traits? A holistic approach that considers the organismal biology of bacteria with their diverse hosts seems appropriate to begin to tackle such issues. As it happens, the type III secretion system is turning out to be a central player in the adaptation of both parasites and mutualists to diverse hosts. With this in mind, human interventions in agriculture, animal husbandry and even drug discovery that could influence the selection of bacteria with improved type III secretion system function should be critically appraised.200919217298
6508170.9565Synergizing Ecotoxicology and Microbiome Data Is Key for Developing Global Indicators of Environmental Antimicrobial Resistance. The One Health concept recognises the interconnectedness of humans, plants, animals and the environment. Recent research strongly supports the idea that the environment serves as a significant reservoir for antimicrobial resistance (AMR). However, the complexity of natural environments makes efforts at AMR public health risk assessment difficult. We lack sufficient data on key ecological parameters that influence AMR, as well as the primary proxies necessary for evaluating risks to human health. Developing environmental AMR 'early warning systems' requires models with well-defined parameters. This is necessary to support the implementation of clear and targeted interventions. In this review, we provide a comprehensive overview of the current tools used globally for environmental AMR human health risk assessment and the underlying knowledge gaps. We highlight the urgent need for standardised, cost-effective risk assessment frameworks that are adaptable across different environments and regions to enhance comparability and reliability. These frameworks must also account for previously understudied AMR sources, such as horticulture, and emerging threats like climate change. In addition, integrating traditional ecotoxicology with modern 'omics' approaches will be essential for developing more comprehensive risk models and informing targeted AMR mitigation strategies.202439611949
6656180.9564Understanding the Evolution and Transmission Dynamics of Antibiotic Resistance Genes: A Comprehensive Review. Antibiotic resistance poses a formidable challenge to global public health, necessitating comprehensive understanding and strategic interventions. This review explores the evolution and transmission dynamics of antibiotic resistance genes, with a focus on Bangladesh. The indiscriminate use of antibiotics, compounded by substandard formulations and clinical misdiagnosis, fuels the emergence and spread of resistance in the country. Studies reveal high resistance rates among common pathogens, emphasizing the urgent need for targeted interventions and rational antibiotic use. Molecular assessments uncover a diverse array of antibiotic resistance genes in environmental reservoirs, highlighting the complex interplay between human activities and resistance dissemination. Horizontal gene transfer mechanisms, particularly plasmid-mediated conjugation, facilitate the exchange of resistance determinants among bacterial populations, driving the evolution of multidrug-resistant strains. The review discusses clinical implications, emphasizing the interconnectedness of environmental and clinical settings in resistance dynamics. Furthermore, bioinformatic and experimental evidence elucidates novel mechanisms of resistance gene transfer, underscoring the dynamic nature of resistance evolution. In conclusion, combating antibiotic resistance requires a multifaceted approach, integrating surveillance, stewardship, and innovative research to preserve the efficacy of antimicrobial agents and safeguard public health.202439113256
8181190.9564Bacterial resistance to antibacterial agents: Mechanisms, control strategies, and implications for global health. The spread of bacterial drug resistance has posed a severe threat to public health globally. Here, we cover bacterial resistance to current antibacterial drugs, including traditional herbal medicines, conventional antibiotics, and antimicrobial peptides. We summarize the influence of bacterial drug resistance on global health and its economic burden while highlighting the resistance mechanisms developed by bacteria. Based on the One Health concept, we propose 4A strategies to combat bacterial resistance, including prudent Application of antibacterial agents, Administration, Assays, and Alternatives to antibiotics. Finally, we identify several opportunities and unsolved questions warranting future exploration for combating bacterial resistance, such as predicting genetic bacterial resistance through the use of more effective techniques, surveying both genetic determinants of bacterial resistance and the transmission dynamics of antibiotic resistance genes (ARGs).202336435256