Recent advances in gene-editing approaches for tackling antibiotic resistance threats: a review. - Related Documents




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918701.0000Recent advances in gene-editing approaches for tackling antibiotic resistance threats: a review. Antibiotic resistance, a known global health challenge, involves the flow of bacteria and their genes among animals, humans, and their surrounding environment. It occurs when bacteria evolve and become less responsive to the drugs designated to kill them, making infections harder to treat. Despite several obstacles preventing the spread of genes and bacteria, pathogens regularly acquire novel resistance factors from other species, which reduces their ability to prevent and treat such bacterial infections. This issue requires coordinated efforts in healthcare, research, and public awareness to address its impact on human health worldwide. This review outlines how recent advances in gene editing technology, especially CRISPR/Cas9, unveil a breakthrough in combating antibiotic resistance. Our focus will remain on the relationship between CRISPR/cas9 and its impact on antibiotic resistance and its related infections. Moreover, the prospects of this new advanced research and the challenges of adopting these technologies against infections will be outlined by exploring its different derivatives and discussing their advantages and limitations over others, thereby providing a corresponding reference for the control and prevention of the spread of antibiotic resistance.202438994001
918810.9999CRISPR-Cas system, antibiotic resistance and virulence in bacteria: Through a common lens. CRISPR-Cas system, antibiotic resistance and virulence are different modes of survival for the bacteria. CRISPR-Cas is an adaptive immune system that can degrade foreign DNA, antibiotic resistance helps bacteria to evade drugs that can threaten their existence and virulence determinants are offensive tools that can facilitate the establishment of infection by pathogens. This chapter focuses on these three aspects, providing insights about the CRISPR system and resistance mechanisms in brief, followed by understanding the synergistic or antagonistic relationship of resistance and virulence determinants in connection to the CRISPR system. We have addressed the discussion of this evolving topic through specific examples and studies. Different approaches for successful detection of this unique defense system in bacteria and various applications of the CRISPR-Cas systems to show how it can be harnessed to tackle the increasing problem of antibiotic resistance have been put forth. World Health Organization has declared antibiotic resistance as a serious global problem of the 21st century. As antibiotic-resistant bacteria increase their footprint across the globe, newer tools such as the CRISPR-Cas system hold immense promise to tackle this problem.202133685595
948420.9999Phage-antibiotic combinations: a promising approach to constrain resistance evolution in bacteria. Antibiotic resistance has reached dangerously high levels throughout the world. A growing number of bacteria pose an urgent, serious, and concerning threat to public health. Few new antibiotics are available to clinicians and only few are in development, highlighting the need for new strategies to overcome the antibiotic resistance crisis. Combining existing antibiotics with phages, viruses the infect bacteria, is an attractive and promising alternative to standalone therapies. Phage-antibiotic combinations have been shown to suppress the emergence of resistance in bacteria, and sometimes even reverse it. Here, we discuss the mechanisms by which phage-antibiotic combinations reduce resistance evolution, and the potential limitations these mechanisms have in steering microbial resistance evolution in a desirable direction. We also emphasize the importance of gaining a better understanding of mechanisms behind physiological and evolutionary phage-antibiotic interactions in complex in-patient environments.202133175408
817830.9999Unraveling 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
955840.9999Antimicrobial Resistance: Enzymes, Proteins, and Computational Resources. Antimicrobial resistance (AMR) is an important health concern rooted in antibiotic misuse and overuse, resulting in drug-resistant bacteria. However, resistance to these antimicrobials developed as soon as they were administered. Several variables lead to the progression of antimicrobial resistance (AMR), making it a multifaceted challenge for healthcare systems worldwide, such as erroneous diagnosis, inappropriate prescription, incomplete treatment, and many more. Getting an in-depth idea about the mechanism underlying AMR development is essential to overcome this. This review aims to provide information on how various enzymes or proteins aid in the antimicrobial resistance mechanisms and also highlight the clinical perspective of AMR, emphasizing its growing impact on patient outcomes, and incorporate the latest recent data from the World Health Organisation (WHO), underscoring the global urgency of the AMR crisis, with specific attention to trends observed in recent years. Additionally, it is intended to provide ideas about inhibitors that can inhibit the mechanism of antibiotic resistance and also to provide an idea about numerous computational resources available that can be employed to predict genes and/or proteins and enzymes involved in various antibiotic resistance mechanisms.202540770471
918650.9999From Gene Editing to Biofilm Busting: CRISPR-CAS9 Against Antibiotic Resistance-A Review. In recent decades, the development of novel antimicrobials has significantly slowed due to the emergence of antimicrobial resistance (AMR), intensifying the global struggle against infectious diseases. Microbial populations worldwide rapidly develop resistance due to the widespread use of antibiotics, primarily targeting drug-resistant germs. A prominent manifestation of this resistance is the formation of biofilms, where bacteria create protective layers using signaling pathways such as quorum sensing. In response to this challenge, the CRISPR-Cas9 method has emerged as a ground-breaking strategy to counter biofilms. Initially identified as the "adaptive immune system" of bacteria, CRISPR-Cas9 has evolved into a state-of-the-art genetic engineering tool. Its exceptional precision in altering specific genes across diverse microorganisms positions it as a promising alternative for addressing antibiotic resistance by selectively modifying genes in diverse microorganisms. This comprehensive review concentrates on the historical background, discovery, developmental stages, and distinct components of CRISPR Cas9 technology. Emphasizing its role as a widely used genome engineering tool, the review explores how CRISPR Cas9 can significantly contribute to the targeted disruption of genes responsible for biofilm formation, highlighting its pivotal role in reshaping strategies to combat antibiotic resistance and mitigate the challenges posed by biofilm-associated infectious diseases.202438702575
817160.9999Advancements 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
944270.9999Antibiotic resistance. Antibiotic resistance poses serious challenges to health and national security, and policy changes will be required to mitigate the consequences of antibiotic resistance. Resistance can arise in disease-causing bacteria naturally, or it can be deliberately introduced to a biological weapon. In either case, life-saving drugs are rendered ineffective. Resistant bacterial infections are difficult to treat, and there are few new antibiotics in the drug development pipeline. This article describes how antibiotic resistance affects health and national security, how bacteria become antibiotic resistant, and what should be done now so antibiotics will be available to save lives in the future.200920028245
944380.9999Is Genetic Mobilization Considered When Using Bacteriophages in Antimicrobial Therapy? The emergence of multi-drug resistant bacteria has undermined our capacity to control bacterial infectious diseases. Measures needed to tackle this problem include controlling the spread of antibiotic resistance, designing new antibiotics, and encouraging the use of alternative therapies. Phage therapy seems to be a feasible alternative to antibiotics, although there are still some concerns and legal issues to overcome before it can be implemented on a large scale. Here we highlight some of those concerns, especially those related to the ability of bacteriophages to transport bacterial DNA and, in particular, antibiotic resistance genes.201729206153
919090.9999Phage-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
8180100.9999Harnessing 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
8179110.9998Nanotechnology 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
9444120.9998Prospects for the Use of New Technologies to Combat Multidrug-Resistant Bacteria. The increasing use of antibiotics is being driven by factors such as the aging of the population, increased occurrence of infections, and greater prevalence of chronic diseases that require antimicrobial treatment. The excessive and unnecessary use of antibiotics in humans has led to the emergence of bacteria resistant to the antibiotics currently available, as well as to the selective development of other microorganisms, hence contributing to the widespread dissemination of resistance genes at the environmental level. Due to this, attempts are being made to develop new techniques to combat resistant bacteria, among them the use of strictly lytic bacteriophage particles, CRISPR-Cas, and nanotechnology. The use of these technologies, alone or in combination, is promising for solving a problem that humanity faces today and that could lead to human extinction: the domination of pathogenic bacteria resistant to artificial drugs. This prospective paper discusses the potential of bacteriophage particles, CRISPR-Cas, and nanotechnology for use in combating human (bacterial) infections.201931293420
9185130.9998The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications? Extended overuse and misuse of antibiotics and other antibacterial agents has resulted in an antimicrobial resistance crisis. Bacteriophages, viruses that infect bacteria, have emerged as a legitimate alternative antibacterial agent with a wide scope of applications which continue to be discovered and refined. However, the potential of some bacteriophages to aid in the acquisition, maintenance, and dissemination of negatively associated bacterial genes, including resistance and virulence genes, through transduction is of concern and requires deeper understanding in order to be properly addressed. In particular, their ability to interact with mobile genetic elements such as plasmids, genomic islands, and integrative conjugative elements (ICEs) enables bacteriophages to contribute greatly to bacterial evolution. Nonetheless, bacteriophages have the potential to be used as therapeutic and biocontrol agents within medical, agricultural, and food processing settings, against bacteria in both planktonic and biofilm environments. Additionally, bacteriophages have been deployed in developing rapid, sensitive, and specific biosensors for various bacterial targets. Intriguingly, their bioengineering capabilities show great promise in improving their adaptability and effectiveness as biocontrol and detection tools. This review aims to provide a balanced perspective on bacteriophages by outlining advantages, challenges, and future steps needed in order to boost their therapeutic and biocontrol potential, while also providing insight on their potential role in contributing to bacterial evolution and survival.202133670836
9184140.9998Unlocking the potential of phages: Innovative approaches to harnessing bacteriophages as diagnostic tools for human diseases. Phages, viruses that infect bacteria, have been explored as promising tools for the detection of human disease. By leveraging the specificity of phages for their bacterial hosts, phage-based diagnostic tools can rapidly and accurately detect bacterial infections in clinical samples. In recent years, advances in genetic engineering and biotechnology have enabled the development of more sophisticated phage-based diagnostic tools, including those that express reporter genes or enzymes, or target specific virulence factors or antibiotic resistance genes. However, despite these advancements, there are still challenges and limitations to the use of phage-based diagnostic tools, including concerns over phage safety and efficacy. This review aims to provide a comprehensive overview of the current state of phage-based diagnostic tools, including their advantages, limitations, and potential for future development. By addressing these issues, we hope to contribute to the ongoing efforts to develop safe and effective phage-based diagnostic tools for the detection of human disease.202337770168
9533150.9998The disparate effects of bacteriophages on antibiotic-resistant bacteria. Faced with the crisis of multidrug-resistant bacteria, bacteriophages, viruses that infect and replicate within bacteria, have been reported to have both beneficial and detrimental effects with respect to disease management. Bacteriophages (phages) have important ecological and evolutionary impacts on their bacterial hosts and have been associated with therapeutic use to kill bacterial pathogens, but can lead to the transmission of antibiotic resistance. Although the process known as transduction has been reported for many bacterial species by classic and modern genetic approaches, its contribution to the spread of antibiotic resistance in nature remains unclear. In addition, detailed molecular studies have identified phages residing in bacterial genomes, revealing unexpected interactions between phages and their bacterial hosts. Importantly, antibiotics can induce the production of phages and phage-encoded products, disseminating these viruses and virulence-related genes, which have dangerous consequences for disease severity. These unwanted side-effects of antibiotics cast doubt on the suitability of some antimicrobial treatments and may require new strategies to prevent and limit the selection for virulence. Foremost among these treatments is phage therapy, which could be used to treat many bacterial infectious diseases and confront the pressing problem of antibiotic resistance in pathogenic bacteria. This review discusses the interactions between bacteriophages, antibiotics, and bacteria and provides an integrated perspective that aims to inspire the development of successful antibacterial therapies.201830302018
9585160.9998When Humans Met Superbugs: Strategies to Tackle Bacterial Resistances to Antibiotics. Bacterial resistance to antibiotics poses enormous health and economic burdens to our society, and it is of the essence to explore old and new ways to deal with these problems. Here we review the current status of multi-resistance genes and how they spread among bacteria. We discuss strategies to deal with resistant bacteria, namely the search for new targets and the use of inhibitors of protein-protein interactions, fragment-based methods, or modified antisense RNAs. Finally, we discuss integrated approaches that consider bacterial populations and their niches, as well as the role of global regulators that activate and/or repress the expression of multiple genes in fluctuating environments and, therefore, enable resistant bacteria to colonize new niches. Understanding how the global regulatory circuits work is, probably, the best way to tackle bacterial resistance.201830811343
8181170.9998Bacterial 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
9488180.9998Minimizing potential resistance: the molecular view. The major contribution of molecular biology to the study of antibiotic resistance has been the elucidation of nearly all biochemical mechanisms of resistance and the routes for dissemination of genetic information among bacteria. In this review, we consider the potential contribution of molecular biology to counteracting the evolution of resistant bacteria. In particular, we emphasize the fact that fundamental approaches have had direct practical effects on minimizing potential resistance: by improving interpretation of resistance phenotypes, by providing more adequate human therapy, by fostering more prudent use of antibiotics, and by allowing the rational design of new drugs that evade existing resistance mechanisms or address unexploited targets.200111524711
6675190.9998Genomic Insights into Bacterial Antimicrobial Resistance Transmission and Mitigation Strategies. The rapid emergence and global spread of antimicrobial resistance in recent years have raised significant concerns about the future of modern medicine. Superbugs and multidrugresistant bacteria have become endemic in many parts of the world, raising the specter of untreatable infections. The overuse and misuse of antimicrobials over the past 80 years have undoubtedly contributed to the development of antimicrobial resistance, placing immense pressure on healthcare systems worldwide. Nonetheless, the molecular mechanisms underlying antimicrobial resistance in bacteria have existed since ancient times. Some of these mechanisms and processes have served as the precursors of current resistance determinants, highlighting the ongoing arms race between bacteria and their antimicrobial adversaries. Moreover, the environment harbors many putative resistance genes, yet we cannot still predict which of these genes will emerge and manifest as pathogenic resistance phenotypes. The presence of antibiotics in natural habitats, even at sub-inhibitory concentrations, may provide selective pressures that favor the emergence of novel antimicrobial resistance apparatus and, thus, underscores the need for a comprehensive understanding of the factors driving the persistence and spread of antimicrobial resistance. As the development of antimicrobial strategies that evade resistance is urgently needed, a clear perception of these critical factors could ultimately pave the way for the design of innovative therapeutic targets.202439021167