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816100.9959Integrative 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
815910.9958Quaternary 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
817620.9957Overcoming 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
815830.9957Nanobioconjugates: 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
914140.9956Metallic Nanoparticles-Friends or Foes in the Battle against Antibiotic-Resistant Bacteria? The rapid spread of antibiotic resistances among bacteria demands novel strategies for infection control, and metallic nanoparticles appear as promising tools because of their unique size and tunable properties that allow their antibacterial effects to be maximized. Furthermore, their diverse mechanisms of action towards multiple cell components have suggested that bacteria could not easily develop resistance against nanoparticles. However, research published over the last decade has proven that bacteria can indeed evolve stable resistance mechanisms upon continuous exposure to metallic nanoparticles. In this review, we summarize the currently known individual and collective strategies employed by bacteria to cope with metallic nanoparticles. Importantly, we also discuss the adverse side effects that bacterial exposure to nanoparticles may have on antibiotic resistance dissemination and that might constitute a challenge for the implementation of nanoparticles as antibacterial agents. Overall, studies discussed in this review point out that careful management of these very promising antimicrobials is necessary to preserve their efficacy for infection control.202133673231
917450.9955Developing 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
919060.9955Phage-based biocontrol strategies and their application in agriculture and aquaculture. Meeting global food demands for a growing human population with finite natural resources is a major challenge. Aquaculture and agriculture are critical to satisfy food requirements, yet suffer significant losses from bacterial diseases. Therefore, there is an urgent need to develop novel antimicrobial strategies, which is heightened by increasing antibiotic resistance. Bacteriophages (phages) are viruses that specifically infect bacteria, and phage-derived therapies are promising treatments in the fight against bacterial diseases. Here, we describe multiple ways that phages and phage-based technologies can be used as antimicrobials. Antimicrobial activity can be achieved through lysis of targeted bacteria by virulent phages or lytic enzymes. Alternatively, phages can be engineered for the delivery of lethal genes and other cargoes to kill bacteria and to manipulate the bacterial response to conventional antibiotics. We also briefly highlight research exploring phages as potential biocontrol agents with examples from agriculture and aquaculture.201830514766
914270.9955Mechanism of antibacterial phytoconstituents: an updated review. The increase of multiple drug resistance bacteria significantly diminishes the effectiveness of antibiotic armory and subsequently exaggerates the level of therapeutic failure. Phytoconstituents are exceptional substitutes for resistance-modifying vehicles. The plants appear to be a deep well for the discovery of novel antibacterial compounds. This is owing to the numerous enticing characteristics of plants, they are easily accessible and inexpensive, extracts or chemicals derived from plants typically have significant levels of action against infections, and they rarely cause serious adverse effects. The enormous selection of phytochemicals offers very distinct chemical structures that may provide both novel mechanisms of antimicrobial activity and deliver us with different targets in the interior of the bacterial cell. They can directly affect bacteria or act together with the crucial events of pathogenicity, in this manner decreasing the aptitude of bacteria to create resistance. Abundant phytoconstituents demonstrate various mechanisms of action toward multi drug resistance bacteria. Overall, this comprehensive review will provide insights into the potential of phytoconstituents as alternative treatments for bacterial infections, particularly those caused by multi drug resistance strains. By examining the current state of research in this area, the review will shed light on potential future directions for the development of new antimicrobial therapies.202438913205
818080.9955Harnessing Nanoparticles to Overcome Antimicrobial Resistance: Promises and Challenges. The rise of antimicrobial resistance (AMR) has become a serious global health issue that kills millions of people each year globally. AMR developed in bacteria is difficult to treat and poses a challenge to clinicians. Bacteria develop resistance through a variety of processes, including biofilm growth, targeted area alterations, and therapeutic drug alteration, prolonging the period they remain within cells, where antibiotics are useless at therapeutic levels. This rise in resistance is linked to increased illness and death, highlighting the urgent need for effective solutions to combat this growing challenge. Nanoparticles (NPs) offer unique solutions for fighting AMR bacteria. Being smaller in size with a high surface area, enhancing interaction with bacteria makes the NPs strong antibacterial agents against various infections. In this review, we have discussed the epidemiology and mechanism of AMR development. Furthermore, the role of nanoparticles as antibacterial agents, and their role in drug delivery has been addressed. Additionally, the potential, challenges, toxicity, and future prospects of nanoparticles as antibacterial agents against AMR pathogens have been discussed. The research work discussed in this review links with Sustainable Development Goal 3 (SDG-3), which aims to ensure disease-free lives and promote well-being for all ages.202539219123
817890.9954Unraveling 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
8162100.9954Nanotechnology 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
9182110.9954Harnessing CRISPR/Cas9 in engineering biotic stress immunity in crops. There is significant potential for CRISPR/Cas9 to be used in developing crops that can adapt to biotic stresses such as fungal, bacterial, viral, and pest infections and weeds. The increasing global population and climate change present significant threats to food security by putting stress on plants, making them more vulnerable to diseases and productivity losses caused by pathogens, pests, and weeds. Traditional breeding methods are inadequate for the rapid development of new plant traits needed to counteract this decline in productivity. However, modern advances in genome-editing technologies, particularly CRISPR/Cas9, have transformed crop protection through precise and targeted modifications of plant genomes. This enables the creation of resilient crops with improved resistance to pathogens, pests, and weeds. This review examines various methods by which CRISPR/Cas9 can be utilized for crop protection. These methods include knocking out susceptibility genes, introducing resistance genes, and modulating defense genes. Potential applications of CRISPR/Cas9 in crop protection involve introducing genes that confer resistance to pathogens, disrupting insect genes responsible for survival and reproduction, and engineering crops that are resistant to herbicides. In conclusion, CRISPR/Cas9 holds great promise for advancing crop protection and ensuring food security in the face of environmental challenges and increasing population pressures. The most recent advancements in CRISPR technology for creating resistance to bacteria, fungi, viruses, and pests are covered here. We wrap up by outlining the most pressing issues and technological shortcomings, as well as unanswered questions for further study.202540663257
9539120.9953Materials for restoring lost Activity: Old drugs for new bugs. The escalation of bacterial resistance to conventional medical antibiotics is a serious concern worldwide. Improvements to current therapies are urgently needed to address this problem. The synergistic combination of antibiotics with other agents is a strategic solution to combat multi-drug-resistant bacteria. Although these combinations decrease the required high dosages and therefore, reduce the toxicity of both agents without compromising the bactericidal effect, they cannot stop the development of further resistance. Recent studies have shown certain elements restore the ability of antibiotics to destroy bacteria that have acquired resistance to them. Due to these synergistic activities, organic and inorganic molecules have been investigated with the goal of restoring antibiotics in new approaches that mitigate the risk of expanding resistance. Herein, we summarize recent studies that restore antibiotics once thought to be ineffective, but have returned to our armamentarium through innovative, combinatorial efforts. A special focus is placed on the mechanisms that allow the synergistic combinations to combat bacteria. The promising data that demonstrated restoration of antimicrobials, supports the notion to find more combinations that can combat antibiotic-resistant bacteria.202235461913
9192130.9953Antimicrobial peptides: Sustainable application informed by evolutionary constraints. The proliferation and global expansion of multidrug-resistant (MDR) bacteria have deepened the need to develop novel antimicrobials. Antimicrobial peptides (AMPs) are regarded as promising antibacterial agents because of their broad-spectrum antibacterial activity and multifaceted mechanisms of action with non-specific targets. However, if AMPs are to be applied sustainably, knowledge of how they induce resistance in pathogenic bacteria must be mastered to avoid repeating the traditional antibiotic resistance mistakes currently faced. Furthermore, the evolutionary constraints on the acquisition of AMP resistance by microorganisms in the natural environment, such as functional compatibility and fitness trade-offs, inform the translational application of AMPs. Consequently, the shortcut to achieve sustainable utilization of AMPs is to uncover the evolutionary constraints of bacteria on AMP resistance in nature and find the tricks to exploit these constraints, such as applying AMP cocktails to minimize the efficacy of selection for resistance or combining nanomaterials to maximize the costs of AMP resistance. Altogether, this review dissects the benefits, challenges, and opportunities of utilizing AMPs against disease-causing bacteria, and highlights the use of AMP cocktails or nanomaterials to proactively address potential AMP resistance crises in the future.202235752270
9143140.9953Bacteria in cancer therapy: A new generation of weapons. Tumors are presently a major threat to human life and health. Malignant tumors are conventionally treated through radiotherapy and chemotherapy. However, traditional therapies yield unsatisfactory results due to high toxicity to the normal cells, inability to treat deep tumor tissues, and the possibility of inducing drug resistance in the tumor cells. This has caused immunotherapy to emerge as an effective and alternate treatment strategy. To overcome the limitations of the conventional treatments as well as to avert the risk of various drug resistance and cytotoxicity, bacterial anti-tumor immunotherapy has raised the interest of researchers. This therapeutic strategy employs bacteria to specifically target and colonize the tumor tissues with preferential accumulation and proliferation. Such bacterial accumulation initiates a series of anti-tumor immune responses, effectively eliminating the tumor cells. This immunotherapy can use the bacteria alone or concomitantly with the other methods. For example, the bacteria can deliver the anti-cancer effect mediators by regulating the expression of the bacterial genes or by synthesizing the bioengineered bacterial complexes. This review will discuss the mechanism of utilizing bacteria in treating tumors, especially in terms of immune mechanisms. This could help in better integrating the bacterial method with other treatment options, thereby, providing a more effective, reliable, and unique treatment therapy for tumors.202235522104
8163150.9953Green 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
8179160.9953Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives. The wide spread of antibiotic resistance has been alarming in recent years and poses a serious global hazard to public health as it leads to millions of deaths all over the world. The wide spread of resistance and sharing resistance genes between different types of bacteria led to emergence of multidrug resistant (MDR) microorganisms. This problem is exacerbated when microorganisms create biofilms, which can boost bacterial resistance by up to 1000-fold and increase the emergence of MDR infections. The absence of novel and potent antimicrobial compounds is linked to the rise of multidrug resistance. This has sparked international efforts to develop new and improved antimicrobial agents as well as innovative and efficient techniques for antibiotic administration and targeting. There is an evolution in nanotechnology in recent years in treatment and prevention of the biofilm formation and MDR infection. The development of nanomaterial-based therapeutics, which could overcome current pathways linked to acquired drug resistance, is a hopeful strategy for treating difficult-to-treat bacterial infections. Additionally, nanoparticles' distinct size and physical characteristics enable them to target biofilms and treat resistant pathogens. This review highlights the current advances in nanotechnology to combat MDR and biofilm infection. In addition, it provides insight on development and mechanisms of antibiotic resistance, spread of MDR and XDR infection, and development of nanoparticles and mechanisms of their antibacterial activity. Moreover, this review considers the difference between free antibiotics and nanoantibiotics, and the synergistic effect of nanoantibiotics to combat planktonic bacteria, intracellular bacteria and biofilm. Finally, we will discuss the strength and limitations of the application of nanotechnology against bacterial infection and future perspectives.202336830949
9181170.9952All Roads Lead to Rome: Pathways to Engineering Disease Resistance in Plants. Unlike animals, plants are unable to move and lack specialized immune cells and circulating antibodies. As a result, they are always threatened by a large number of microbial pathogens and harmful pests that can significantly reduce crop yield worldwide. Therefore, the development of new strategies to control them is essential to mitigate the increasing risk of crops lost to plant diseases. Recent developments in genetic engineering, including efficient gene manipulation and transformation methods, gene editing and synthetic biology, coupled with the understanding of microbial pathogenicity and plant immunity, both at molecular and genomic levels, have enhanced the capabilities to develop disease resistance in plants. This review comprehensively explains the fundamental mechanisms underlying the tug-of-war between pathogens and hosts, and provides a detailed overview of different strategies for developing disease resistance in plants. Additionally, it provides a summary of the potential genes that can be employed in resistance breeding for key crops to combat a wide range of potential pathogens and pests, including fungi, oomycetes, bacteria, viruses, nematodes, and insects. Furthermore, this review addresses the limitations associated with these strategies and their possible solutions. Finally, it discusses the future perspectives for producing plants with durable and broad-spectrum disease resistance.202539691979
6682180.9952Antibiotic resistance in agriculture: Perspectives on upcoming strategies to overcome upsurge in resistance. Antibiotic resistance is a massive problem rising constantly and spreading rapidly since the past decade. The major underlying mechanism responsible for this problem is an overuse or severe misuse of antibiotics. Regardless of this emerging global threat, antibiotics are still being widely used, not only for treatment of human infections, but also to a great extent in agriculture, livestock and animal husbandry. If the current scenario persists, we might enter into a post-antibiotic era where drugs might not be able to treat even the simplest of infections. This review discusses the current status of antibiotic utilization and molecular basis of antibiotic resistance mechanisms acquired by bacteria, along with the modes of transmittance of the resultant resistant genes into human pathogens through their cycling among different ecosystems. The main focus of the article is to provide an insight into the different molecular and other strategies currently being studied worldwide for their use as an alternate to antibiotics with an overall aim to overcome or minimize the global problem of antibiotic resistance.202134841321
8172190.9952From resistance to remedy: the role of clustered regularly interspaced short palindromic repeats system in combating antimicrobial resistance-a review. The growing challenge of antimicrobial resistance (AMR) poses a significant and increasing risk to public health worldwide, necessitating innovative strategies to restore the efficacy of antibiotics. The precise genome-editing abilities of the CRISPR-Cas system have made it a potent instrument for directly targeting and eliminating antibiotic resistance genes. This review explored the mechanisms and applications of CRISPR-Cas systems in combating AMR. The latest developments in CRISPR technology have broadened its potential use, encompassing programmable antibacterial agents and improved diagnostic methods for antibiotic-resistant infections. Nevertheless, several challenges must be overcome for clinical success, including the survival of resistant bacteria, generation of anti-CRISPR proteins that reduce effectiveness, and genetic modifications that change target sequences. Additionally, the efficacy of CRISPR-Cas systems differs across bacterial species, making their universal application challenging. After overcoming these challenges, CRISPR-Cas has the potential to revolutionize AMR treatment, restore antibiotic efficacy, and reshape infection control.202539404843