# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8174 | 0 | 0.9917 | Recent Advances in Understanding the Molecular Mechanisms of Multidrug Resistance and Novel Approaches of CRISPR/Cas9-Based Genome-Editing to Combat This Health Emergency. The rapid spread of multidrug resistance (MDR), due to abusive use of antibiotics has led to global health emergency, causing substantial morbidity and mortality. Bacteria attain MDR by different means such as antibiotic modification/degradation, target protection/modification/bypass, and enhanced efflux mechanisms. The classical approaches of counteracting MDR bacteria are expensive and time-consuming, thus, it is highly significant to understand the molecular mechanisms of this resistance to curb the problem from core level. The revolutionary approach of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated sequence 9 (CRISPR/Cas9), considered as a next-generation genome-editing tool presents an innovative opportunity to precisely target and edit bacterial genome to alter their MDR strategy. Different bacteria possessing antibiotic resistance genes such as mecA, ermB, ramR, tetA, mqrB and bla(KPC) that have been targeted by CRISPR/Cas9 to re-sensitize these pathogens against antibiotics, such as methicillin, erythromycin, tigecycline, colistin and carbapenem, respectively. The CRISPR/Cas9 from S. pyogenes is the most widely studied genome-editing tool, consisting of a Cas9 DNA endonuclease associated with tracrRNA and crRNA, which can be systematically coupled as sgRNA. The targeting strategies of CRISPR/Cas9 to bacterial cells is mediated through phage, plasmids, vesicles and nanoparticles. However, the targeting approaches of this genome-editing tool to specific bacteria is a challenging task and still remains at a very preliminary stage due to numerous obstacles awaiting to be solved. This review elaborates some recent updates about the molecular mechanisms of antibiotic resistance and the innovative role of CRISPR/Cas9 system in modulating these resistance mechanisms. Furthermore, the delivery approaches of this genome-editing system in bacterial cells are discussed. In addition, some challenges and future prospects are also described. | 2024 | 38344439 |
| 9808 | 1 | 0.9915 | Understanding Recent Developments in Colistin Resistance: Mechanisms, Clinical Implications, and Future Perspectives. Colistin resistance, driven by chromosomal mutations and the spread of plasmid-mediated MCR genes, has emerged as a critical challenge in combating multidrug-resistant Gram-negative bacteria. This resistance compromises the efficacy of colistin, leading to higher treatment failure rates, prolonged hospitalizations, and increased mortality. Recent studies have highlighted key mechanisms, including lipid A modifications, that enable bacteria to evade colistin's effects. The global spread of MCR genes exacerbates the issue, underlining the need for improved diagnostics and rapid detection of resistant strains to prevent adverse patient outcomes. To combat this growing threat, a multifaceted approach is essential, involving enhanced antimicrobial stewardship, stricter infection control measures, and continued research into alternative therapies and diagnostic methods. Collaborative efforts from researchers, healthcare providers, policymakers, and the pharmaceutical industry are crucial to preserving colistin's effectiveness and mitigating the broader impact on public health. | 2025 | 41148650 |
| 6650 | 2 | 0.9915 | Antibiotic resistance is never going to go away. No matter how many drugs we throw at it, no matter how much money and resources are sacrificed to wage a war on resistance, it will always prevail. Humans are forced to coexist with the fact of antibiotic resistance. Public health officials, clinicians, and scientists must find effective ways to cope with antibiotic resistant bacteria harmful to humans and animals and to control the development of new types of resistance. The American Academy of Microbiology convened a colloquium October 12–14, 2008, to discuss antibiotic resistance and the factors that influence the development and spread of resistance. Participants, whose areas of expertise included medicine, microbiology, and public health, made specific recommendations for needed research, policy development, a surveillance network, and treatment guidelines. Antibiotic resistance issues specific to the developing world were discussed and recommendations for improvements were made. Each antibiotic is injurious only to a certain segment of the microbial world, so for a given antibacterial there are some species of bacteria that are susceptible and others not. Bacterial species insusceptible to a particular drug are “naturally resistant.” Species that were once sensitive but eventually became resistant to it are said to have “acquired resistance.” It is important to note that “acquired resistance” affects a subset of strains in the entire species; that is why the prevalence of “acquired resistance” in a species is different according to location. Antibiotic resistance, the acquired ability of a pathogen to withstand an antibiotic that kills off its sensitive counterparts, originally arises from random mutations in existing genes or from intact genes that already serve a similar purpose. Exposure to antibiotics and other antimicrobial products, whether in the human body, in animals, or the environment, applies selective pressure that encourages resistance to emerge favoring both “naturally resistant” strains and strains which have “acquired resistance.” Horizontal gene transfer, in which genetic information is passed between microbes, allows resistance determinants to spread within harmless environmental or commensal microorganisms and pathogens, thus creating a reservoir of resistance. Resistance is also spread by the replication of microbes that carry resistance genes, a process that produces genetically identical (or clonal) progeny. Rapid diagnostic methods and surveillance are some of the most valuable tools in preventing the spread of resistance. Access to more rapid diagnostic tests that could determine the causative agent and antibiotic susceptibility of infections would inform better decision making with respect to antibiotic use, help slow the selection of resistant strains in clinical settings, and enable better disease surveillance. A rigorous surveillance network to track the evolution and spread of resistance is also needed and would probably result in significant savings in healthcare. Developing countries face unique challenges when it comes to antibiotic resistance; chief among them may be the wide availability of antibiotics without a prescription and also counterfeit products of dubious quality. Lack of adequate hygiene, poor water quality, and failure to manage human waste also top the list. Recommendations for addressing the problems of widespread resistance in the developing world include: proposals for training and infrastructure capacity building; surveillance programs; greater access to susceptibility testing; government controls on import, manufacture and use; development and use of vaccines; and incentives for pharmaceutical companies to supply drugs to these countries. Controlling antibiotic resistant bacteria and subsequent infections more efficiently necessitates the prudent and responsible use of antibiotics. It is mandatory to prevent the needless use of antibiotics (e.g., viral infections; unnecessary prolonged treatment) and to improve the rapid prescription of appropriate antibiotics to a patient. Delayed or inadequate prescriptions reduce the efficacy of treatment and favor the spread of the infection. Prudent use also applies to veterinary medicine. For example, antibiotics used as “growth promoters” have been banned in Europe and are subject to review in some other countries. There are proven techniques for limiting the spread of resistance, including hand hygiene, but more rapid screening techniques are needed in order to effectively track and prevent spread in clinical settings. The spread of antibiotic resistance on farms and in veterinary hospitals may also be significant and should not be neglected. Research is needed to pursue alternative approaches, including vaccines, antisense therapy, public health initiatives, and others. The important messages about antibiotic resistance are not getting across from scientists and infectious diseases specialists to prescribers, stakeholders, including the public, healthcare providers, and public officials. Innovative and effective communication initiatives are needed, as are carefully tailored messages for each of the stakeholder groups. | 2009 | 32644325 |
| 8173 | 3 | 0.9915 | Advancing Antibacterial Strategies: CRISPR-Phage-Mediated Gene Therapy Targeting Bacterial Resistance Genes. One of the most significant issues facing the world today is antibiotic resistance, which makes it increasingly difficult to treat bacterial infections. Regular antibiotics no longer work against many bacteria, affecting millions of people. A novel approach known as CRISPR-phage therapy may be beneficial. This technique introduces a technology called CRISPR into resistant bacteria using bacteriophages. The genes that cause bacteria to become resistant to antibiotics can be identified and cut using CRISPR. This enables antibiotics to function by inhibiting the bacteria. This approach is highly precise, unlike conventional antibiotics, so it doesn't damage our bodies' beneficial bacteria. Preliminary studies and limited clinical trials suggest that this technique can effectively target drug-resistant bacteria such as Klebsiella pneumoniae and Methicillinresistant Staphylococcus aureus (MRSA). However, challenges in phage engineering, host delivery, and the growing threat of bacterial CRISPR resistance demand urgent and strategic innovation. Our perspective underscores that without proactive resolution of these hurdles, the current hopefulness could disappear. Looking ahead, integrating next-generation Cas effectors, non-DSB editors, and resistance monitoring frameworks could transform CRISPR-phage systems from an experimental novelty into a clinical mainstay. This shift will require not only scientific ingenuity but also coordinated advances in regulatory, translational, and manufacturing efforts. | 2025 | 40990280 |
| 9810 | 4 | 0.9915 | Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies. Antimicrobial resistance in the intensive care unit is an ongoing global healthcare concern associated with high mortality and morbidity rates and high healthcare costs. Select groups of bacterial pathogens express different mechanisms of antimicrobial resistance. Clinicians face challenges in managing patients with multidrug-resistant bacteria in the form of a limited pool of available antibiotics, slow and potentially inaccurate conventional diagnostic microbial modalities, mimicry of non-infective conditions with infective syndromes, and the confounding of the clinical picture of organ dysfunction associated with sepsis with postoperative surgical complications such as hemorrhage and fluid shifts. Potential remedies for antimicrobial resistance include specific surveillance, adequate and systematic antibiotic stewardship, use of pharmacokinetic and pharmacodynamic techniques of therapy, and antimicrobial monitoring and adequate employment of infection control policies. Novel techniques of combating antimicrobial resistance include the use of aerosolized antibiotics for lung infections, the restoration of gut microflora using fecal transplantation, and orally administered probiotics. Newer antibiotics are urgently needed as part of the armamentarium against multidrug-resistant bacteria. In this review we discuss mechanisms and patterns of microbial resistance in a select group of drug-resistant bacteria, and preventive and remedial measures for combating antibiotic resistance in the critically ill. | 2023 | 39816646 |
| 9087 | 5 | 0.9915 | Complementary supramolecular drug associates in perfecting the multidrug therapy against multidrug resistant bacteria. The inappropriate and inconsistent use of antibiotics in combating multidrug-resistant bacteria exacerbates their drug resistance through a few distinct pathways. Firstly, these bacteria can accumulate multiple genes, each conferring resistance to a specific drug, within a single cell. This accumulation usually takes place on resistance plasmids (R). Secondly, multidrug resistance can arise from the heightened expression of genes encoding multidrug efflux pumps, which expel a broad spectrum of drugs from the bacterial cells. Additionally, bacteria can also eliminate or destroy antibiotic molecules by modifying enzymes or cell walls and removing porins. A significant limitation of traditional multidrug therapy lies in its inability to guarantee the simultaneous delivery of various drug molecules to a specific bacterial cell, thereby fostering incremental drug resistance in either of these paths. Consequently, this approach prolongs the treatment duration. Rather than using a biologically unimportant coformer in forming cocrystals, another drug molecule can be selected either for protecting another drug molecule or, can be selected for its complementary activities to kill a bacteria cell synergistically. The development of a multidrug cocrystal not only improves tabletability and plasticity but also enables the simultaneous delivery of multiple drugs to a specific bacterial cell, philosophically perfecting multidrug therapy. By adhering to the fundamental tenets of multidrug therapy, the synergistic effects of these drug molecules can effectively eradicate bacteria, even before they have the chance to develop resistance. This approach has the potential to shorten treatment periods, reduce costs, and mitigate drug resistance. Herein, four hypotheses are presented to create complementary drug cocrystals capable of simultaneously reaching bacterial cells, effectively destroying them before multidrug resistance can develop. The ongoing surge in the development of novel drugs provides another opportunity in the fight against bacteria that are constantly gaining resistance to existing treatments. This endeavour holds the potential to combat a wide array of multidrug-resistant bacteria. | 2024 | 38415251 |
| 9086 | 6 | 0.9915 | Emergence and selection of isoniazid and rifampin resistance in tuberculosis granulomas. Drug resistant tuberculosis is increasing world-wide. Resistance against isoniazid (INH), rifampicin (RIF), or both (multi-drug resistant TB, MDR-TB) is of particular concern, since INH and RIF form part of the standard regimen for TB disease. While it is known that suboptimal treatment can lead to resistance, it remains unclear how host immune responses and antibiotic dynamics within granulomas (sites of infection) affect emergence and selection of drug-resistant bacteria. We take a systems pharmacology approach to explore resistance dynamics within granulomas. We integrate spatio-temporal host immunity, INH and RIF dynamics, and bacterial dynamics (including fitness costs and compensatory mutations) in a computational framework. We simulate resistance emergence in the absence of treatment, as well as resistance selection during INH and/or RIF treatment. There are four main findings. First, in the absence of treatment, the percentage of granulomas containing resistant bacteria mirrors the non-monotonic bacterial dynamics within granulomas. Second, drug-resistant bacteria are less frequently found in non-replicating states in caseum, compared to drug-sensitive bacteria. Third, due to a steeper dose response curve and faster plasma clearance of INH compared to RIF, INH-resistant bacteria have a stronger influence on treatment outcomes than RIF-resistant bacteria. Finally, under combination therapy with INH and RIF, few MDR bacteria are able to significantly affect treatment outcomes. Overall, our approach allows drug-specific prediction of drug resistance emergence and selection in the complex granuloma context. Since our predictions are based on pre-clinical data, our approach can be implemented relatively early in the treatment development process, thereby enabling pro-active rather than reactive responses to emerging drug resistance for new drugs. Furthermore, this quantitative and drug-specific approach can help identify drug-specific properties that influence resistance and use this information to design treatment regimens that minimize resistance selection and expand the useful life-span of new antibiotics. | 2018 | 29746491 |
| 8172 | 7 | 0.9914 | From 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. | 2025 | 39404843 |
| 9224 | 8 | 0.9914 | Plant-derived secondary metabolites as the main source of efflux pump inhibitors and methods for identification. The upsurge of multiple drug resistance (MDR) bacteria substantially diminishes the effectiveness of antibiotic arsenal and therefore intensifies the rate of therapeutic failure. The major factor in MDR is efflux pump-mediated resistance. A unique pump can make bacteria withstand a wide range of structurally diverse compounds. Therefore, their inhibition is a promising route to eliminate resistance phenomenon in bacteria. Phytochemicals are excellent alternatives as resistance-modifying agents. They can directly kill bacteria or interact with the crucial events of pathogenicity, thereby decreasing the ability of bacteria to develop resistance. Numerous botanicals display noteworthy efflux pumps inhibitory activities. Edible plants are of growing interest. Likewise, some plant families would be excellent sources of efflux pump inhibitors (EPIs) including Apocynaceae, Berberidaceae, Convolvulaceae, Cucurbitaceae, Fabaceae, Lamiaceae, and Zingiberaceae. Easily applicable methods for screening plant-derived EPIs include checkerboard synergy test, berberine uptake assay and ethidium bromide test. In silico high-throughput virtual detection can be evaluated as a criterion of excluding compounds with efflux substrate-like characteristics, thereby improving the selection process and extending the identification of EPIs. To ascertain the efflux activity inhibition, real-time PCR and quantitative mass spectrometry can be applied. This review emphasizes on efflux pumps and their roles in transmitting bacterial resistance and an update plant-derived EPIs and strategies for identification. | 2020 | 32923005 |
| 8170 | 9 | 0.9914 | Exploring molecular mechanisms of drug resistance in bacteria and progressions in CRISPR/Cas9-based genome expurgation solutions. Antibiotic resistance in bacteria is a critical global health challenge, driven by molecular mechanisms such as genetic mutations, efflux pumps, enzymatic degradation of antibiotics, target site modifications, and biofilm formation. Horizontal gene transfer (HGT) further accelerates the spread of resistance genes across bacterial populations. These mechanisms contribute to the emergence of multidrug-resistant (MDR) strains, rendering conventional antibiotics ineffective. Recent advancements in CRISPR/Cas9-based genome editing offer innovative solutions to combat drug resistance. CRISPR/Cas9 enables precise targeting of resistance genes, facilitating their deletion or inactivation, and provides a potential method to eliminate resistance-carrying plasmids. Furthermore, phage-delivered CRISPR systems show promise in selectively killing resistant bacteria while leaving susceptible strains unaffected. Despite challenges such as efficient delivery, off-target effects, and potential bacterial resistance to CRISPR itself, ongoing research and technological innovations hold promise for using CRISPR-based antimicrobials to reverse bacterial drug resistance and develop more effective therapies. These abstract highlights the molecular mechanisms underlying bacterial drug resistance and explores how CRISPR/Cas9 technology could revolutionize treatment strategies against resistant pathogens. | 2025 | 40051841 |
| 5098 | 10 | 0.9914 | Feature selection and aggregation for antibiotic resistance GWAS in Mycobacterium tuberculosis: a comparative study. INTRODUCTION: Drug resistance (DR) of pathogens remains a global healthcare concern. In contrast to other bacteria, acquiring mutations in the core genome is the main mechanism of drug resistance for Mycobacterium tuberculosis (MTB). For some antibiotics, the resistance of a particular isolate can be reliably predicted by identifying specific mutations, while for other antibiotics the knowledge of resistance mechanisms is limited. Statistical machine learning (ML) methods are used to infer new genes implicated in drug resistance leveraging large collections of isolates with known whole-genome sequences and phenotypic states for different drugs. However, high correlations between the phenotypic states for commonly used drugs complicate the inference of true associations of mutations with drug phenotypes by ML approaches. METHODS: Recently, several new methods have been developed to select a small subset of reliable predictors of the dependent variable, which may help reduce the number of spurious associations identified. In this study, we evaluated several such methods, namely, logistic regression with different regularization penalty functions, a recently introduced algorithm for solving the best-subset selection problem (ABESS) and "Hungry, Hungry SNPos" (HHS) a heuristic algorithm specifically developed to identify resistance-associated genetic variants in the presence of resistance co-occurrence. We assessed their ability to select known causal mutations for resistance to a specific drug while avoiding the selection of mutations in genes associated with resistance to other drugs, thus we compared selected ML models for their applicability for MTB genome wide association studies. RESULTS AND DISCUSSION: In our analysis, ABESS significantly outperformed the other methods, selecting more relevant sets of mutations. Additionally, we demonstrated that aggregating rare mutations within protein-coding genes into markers indicative of changes in PFAM domains improved prediction quality, and these markers were predominantly selected by ABESS, suggesting their high informativeness. However, ABESS yielded lower prediction accuracy compared to logistic regression methods with regularization. | 2025 | 40606161 |
| 8161 | 11 | 0.9913 | Integrative 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. | 2025 | 40914328 |
| 8166 | 12 | 0.9912 | A Comprehensive Review of Molecular Mechanisms Leading to the Emergence of Multidrug Resistance in Bacteria. Multidrug resistance (MDR) in bacteria poses a serious global health threat, compromising the effectiveness of antibiotics. MDR causes approximately 700,000 deaths annually, with MDR tuberculosis alone claiming 230,000 lives. While bacteria inherently possess intrinsic resistance, acquired resistance stands out as the primary culprit in MDR development. Acquired resistance mechanisms mediated by the bacterial cell wall, nucleic acids, and proteins play a pivotal role in the genesis of MDR. Bacteria can modify their cell wall structure, produce resistant enzymes, exhibit mutations in antibiotic-targeted genes, and acquire resistant genes through horizontal gene transfer. Bacteria can produce proteins that act as enzymes, chemically modifying or directly degrading the antibiotic molecules, leading to the loss of their functionality. Apart from these mechanisms, biofilms also play a pivotal role in MDR expansion. Despite the development of several antibiotics since the discovery of penicillin, continuous structural and molecular modifications in bacteria render these antibiotics ineffective against MDR. The most recent approaches such as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (CRISPR-Cas), nanotechnology, a combination of CRISPR-Cas, and nanoparticles, show promise in treating MDR. Thus, this review delves deep into the molecular mechanisms of MDR, emphasizing the limitations of current antibiotics due to bacterial evolution and highlighting current strategies in the fight against MDR bacteria. This will drive comprehensive research to uncover additional resistance mechanisms and develop innovative strategies to combat resistant bacteria effectively. SUPPLEMENTARY INFORMATION: The online version supplementary material available at 10.1007/s12088-024-01384-6. | 2025 | 40655388 |
| 9813 | 13 | 0.9912 | Antibacterial Discovery: 21st Century Challenges. It has been nearly 50 years since the golden age of antibiotic discovery (1945-1975) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to replace those rendered obsolete by drug resistance. Despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. Obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. This review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering 21st century medicines to combat multidrug resistant pathogens. | 2020 | 32353943 |
| 8171 | 14 | 0.9912 | Advancements 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. | 2025 | 40440869 |
| 8175 | 15 | 0.9912 | Role of Nanocarrier Systems in Drug Delivery for Overcoming Multi-Drug Resistance in Bacteria. Multidrug-resistant (MDR) bacteria have risen alarmingly in the last few decades, posing a serious threat to human health. The need for effective bacterial resistance treatment is urgent and unmet due to the rise in morbidity and mortality that has coincided with the prevalence of infections caused by MDR bacteria. Using its creative and unconventional methods, effective antibiotics for MDR bacteria could be developed using nanomedicine techniques. To combat microbial resistance, a number of strategies have been developed, including the use of natural bactericides, the introduction of fresh antibiotics, the application of combination therapy and the creation of NP-based antibiotic nanocarriers. The absence of novel antibacterial agents has worsened the situation for MDR bacteria. Ineffective antibiotics used to treat MDR bacteria also contribute to the bacteria's tolerance growing. Nanoparticles (NPs) are the most efficient method for eliminating MDR bacteria because they serve as both carriers of natural antibiotics and antimicrobials and active agents against bacteria. Additionally, surface engineering of nanocarriers has important benefits for focusing on and modifying a variety of resistance mechanisms. The use of nanocarrier systems in drug delivery for overcoming bacterial resistance is covered in this review along with various mechanisms of antibiotic resistance. | 2023 | 37480270 |
| 9088 | 16 | 0.9912 | Cocrystallizing and Codelivering Complementary Drugs to Multidrugresistant Tuberculosis Bacteria in Perfecting Multidrug Therapy. Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria. | 2023 | 37150990 |
| 8176 | 17 | 0.9912 | Overcoming 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. | 2021 | 34307323 |
| 9786 | 18 | 0.9912 | The CRISPR/Cas system as an antimicrobial resistance strategy in aquatic ecosystems. With the growing population, demand for food has dramatically increased, and fisheries, including aquaculture, are expected to play an essential role in sustaining demand with adequate quantities of protein and essential vitamin supplements, employment generation, and GDP growth. Unfortunately, the incidence of emerging/re-emerging AMR pathogens annually occurs because of anthropogenic activities and the frequent use of antibiotics in aquaculture. These AMR pathogens include the WHO's top 6 prioritized ESKAPE pathogens (nosocomial pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), extended-spectrum beta lactases (ESBLs) and carbapenemase-producing E. coli, which pose major challenges to the biomagnification of both nonnative and native antibiotic-resistant bacteria in capture and cultured fishes. Although implementing the rational use of antibiotics represents a promising mitigation measure, this approach is practically impossible due to the lack of awareness among farmers about the interplay between antimicrobial use and the emergence of antimicrobial resistance (AMR). Nevertheless, to eradicate these 'superbugs,' CRISPR/Cas (clustered regularly interspersed short palindromic repeats/CRISPR associate protein) has turned out to be a novel approach owing to its ability to perform precise site-directed targeting/knockdown/reversal of specific antimicrobial resistance genes in vitro and to distinguish AMR-resistant bacteria from a plethora of commensal aquatic bacteria. Along with highlighting the importance of virulent multidrug resistance genes in bacteria, this article aims to provide a holistic picture of CRISPR/Cas9-mediated genome editing for combating antimicrobial-resistant bacteria isolated from various aquaculture and marine systems, as well as insights into different types of CRISPR/Cas systems, delivery methods, and challenges associated with developing CRISPR/Cas9 antimicrobial agents. | 2024 | 38806846 |
| 6649 | 19 | 0.9912 | The development of antibiotics has provided much success against infectious diseases in animals and humans. But the intensive and extensive use of antibiotics over the years has resulted in the emergence of drug-resistant bacterial pathogens. The existence of a reservoir(s) of antibiotic resistant bacteria and antibiotic resistance genes in an interactive environment of animals, plants, and humans provides the opportunity for further transfer and dissemination of antibiotic resistance. The emergence of antibiotic resistant bacteria has created growing concern about its impact on animal and human health. To specifically address the impact of antibiotic resistance resulting from the use of antibiotics in agriculture, the American Academy of Microbiology convened a colloquium, “Antibiotic Resistance and the Role of Antimicrobials in Agriculture: A Critical Scientific Assessment,” in Santa Fe, New Mexico, November 2–4, 2001. Colloquium participants included academic, industrial, and government researchers with a wide range of expertise, including veterinary medicine, microbiology, food science, pharmacology, and ecology. These scientists were asked to provide their expert opinions on the current status of antibiotic usage and antibiotic resistance, current research information, and provide recommendations for future research needs. The research areas to be addressed were roughly categorized under the following areas: ▪ Origins and reservoirs of resistance; ▪ Transfer of resistance; ▪ Overcoming/modulating resistance by altering usage; and ▪ Interrupting transfer of resistance. The consensus of colloquium participants was that the evaluation of antibiotic usage and its impact were complex and subject to much speculation and polarization. Part of the complexity stems from the diverse array of animals and production practices for food animal production. The overwhelming consensus was that any use of antibiotics creates the possibility for the development of antibiotic resistance, and that there already exist pools of antibiotic resistance genes and antibiotic resistant bacteria. Much discussion revolved around the measurement of antibiotic usage, the measurement of antibiotic resistance, and the ability to evaluate the impact of various types of usage (animal, human) on overall antibiotic resistance. Additionally, many participants identified commensal bacteria as having a possible role in the continuance of antibiotic resistance as reservoirs. Participants agreed that many of the research questions could not be answered completely because of their complexity and the need for better technologies. The concept of the “smoking gun” to indicate that a specific animal source was important in the emergence of certain antibiotic resistant pathogens was discussed, and it was agreed that ascribing ultimate responsibility is likely to be impossible. There was agreement that expanded and more improved surveillance would add to current knowledge. Science-based risk assessments would provide better direction in the future. As far as preventive or intervention activities, colloquium participants reiterated the need for judicious/prudent use guidelines. Yet they also emphasized the need for better dissemination and incorporation by end-users. It is essential that there are studies to measure the impact of educational efforts on antibiotic usage. Other recommendations included alternatives to antibiotics, such as commonly mentioned vaccines and probiotics. There also was an emphasis on management or production practices that might decrease the need for antibiotics. Participants also stressed the need to train new researchers and to interest students in postdoctoral work, through training grants, periodic workshops, and comprehensive conferences. This would provide the expertise needed to address these difficult issues in the future. Finally, the participants noted that scientific societies and professional organizations should play a pivotal role in providing technical advice, distilling and disseminating information to scientists, media, and consumers, and in increasing the visibility and funding for these important issues. The overall conclusion is that antibiotic resistance remains a complex issue with no simple answers. This reinforces the messages from other meetings. The recommendations from this colloquium provide some insightful directions for future research and action. | 2002 | 32687288 |