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650700.9854What Are the Drivers Triggering Antimicrobial Resistance Emergence and Spread? Outlook from a One Health Perspective. Antimicrobial resistance (AMR) has emerged as a critical global public health threat, exacerbating healthcare burdens and imposing substantial economic costs. Currently, AMR contributes to nearly five million deaths annually worldwide, surpassing mortality rates of any single infectious disease. The economic burden associated with AMR-related disease management is estimated at approximately $730 billion per year. This review synthesizes current research on the mechanisms and multifaceted drivers of AMR development and dissemination through the lens of the One Health framework, which integrates human, animal, and environmental health perspectives. Intrinsic factors, including antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs), enable bacteria to evolve adaptive resistance mechanisms such as enzymatic inactivation, efflux pumps, and biofilm formation. Extrinsic drivers span environmental stressors (e.g., antimicrobials, heavy metals, disinfectants), socioeconomic practices, healthcare policies, and climate change, collectively accelerating AMR proliferation. Horizontal gene transfer and ecological pressures further facilitate the spread of antimicrobial-resistant bacteria across ecosystems. The cascading impacts of AMR threaten human health and agricultural productivity, elevate foodborne infection risks, and impose substantial economic burdens, particularly in low- and middle-income countries. To address this complex issue, the review advocates for interdisciplinary collaboration, robust policy implementation (e.g., antimicrobial stewardship), and innovative technologies (e.g., genomic surveillance, predictive modeling) under the One Health paradigm. Such integrated strategies are essential to mitigate AMR transmission, safeguard global health, and ensure sustainable development.202540558133
665610.9848Understanding the Evolution and Transmission Dynamics of Antibiotic Resistance Genes: A Comprehensive Review. Antibiotic resistance poses a formidable challenge to global public health, necessitating comprehensive understanding and strategic interventions. This review explores the evolution and transmission dynamics of antibiotic resistance genes, with a focus on Bangladesh. The indiscriminate use of antibiotics, compounded by substandard formulations and clinical misdiagnosis, fuels the emergence and spread of resistance in the country. Studies reveal high resistance rates among common pathogens, emphasizing the urgent need for targeted interventions and rational antibiotic use. Molecular assessments uncover a diverse array of antibiotic resistance genes in environmental reservoirs, highlighting the complex interplay between human activities and resistance dissemination. Horizontal gene transfer mechanisms, particularly plasmid-mediated conjugation, facilitate the exchange of resistance determinants among bacterial populations, driving the evolution of multidrug-resistant strains. The review discusses clinical implications, emphasizing the interconnectedness of environmental and clinical settings in resistance dynamics. Furthermore, bioinformatic and experimental evidence elucidates novel mechanisms of resistance gene transfer, underscoring the dynamic nature of resistance evolution. In conclusion, combating antibiotic resistance requires a multifaceted approach, integrating surveillance, stewardship, and innovative research to preserve the efficacy of antimicrobial agents and safeguard public health.202439113256
817120.9844Advancements 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
650830.9842Synergizing Ecotoxicology and Microbiome Data Is Key for Developing Global Indicators of Environmental Antimicrobial Resistance. The One Health concept recognises the interconnectedness of humans, plants, animals and the environment. Recent research strongly supports the idea that the environment serves as a significant reservoir for antimicrobial resistance (AMR). However, the complexity of natural environments makes efforts at AMR public health risk assessment difficult. We lack sufficient data on key ecological parameters that influence AMR, as well as the primary proxies necessary for evaluating risks to human health. Developing environmental AMR 'early warning systems' requires models with well-defined parameters. This is necessary to support the implementation of clear and targeted interventions. In this review, we provide a comprehensive overview of the current tools used globally for environmental AMR human health risk assessment and the underlying knowledge gaps. We highlight the urgent need for standardised, cost-effective risk assessment frameworks that are adaptable across different environments and regions to enhance comparability and reliability. These frameworks must also account for previously understudied AMR sources, such as horticulture, and emerging threats like climate change. In addition, integrating traditional ecotoxicology with modern 'omics' approaches will be essential for developing more comprehensive risk models and informing targeted AMR mitigation strategies.202439611949
816140.9841Integrative 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
817050.9841Exploring 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.202540051841
817860.9840Unraveling 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
955670.9840Recent insights into actinobacteria research in antimicrobial resistance: a review. Antimicrobial resistance (AMR) has emerged as a global health crisis, taking 4.71 million lives in the year 2021 and posing significant challenges to healthcare systems. Actinobacteria, particularly Streptomyces sp., are a well-established source of bioactive secondary metabolites, including antibiotics such as polyketides, aminoglycosides, and macrolides with activity against multidrug-resistant (MDR) bacteria. However, only 10% of the antibiotic genes are expressed, and others are silent in cryptic biosynthetic gene clusters (BGCs) that remain inactive under standard laboratory conditions. Advances in genome mining, bioinformatics tools like antiSMASH, and molecular techniques such as CRISPR-Cas have facilitated the identification of these clusters. Furthermore, innovative strategies such as co-culturing and HDAC inhibitors have shown promise in activating cryptic biosynthetic pathways to combat emerging antimicrobial resistance. Despite these advancements, the rapid evolution of resistance requires continuous research and global collaboration to ensure a sustainable pipeline of effective antibiotics. This review provides insight into actinobacteria-derived antibiotics, resistance mechanisms, and emerging biotechnological interventions to address the AMR crisis, underscoring the urgent need for multidisciplinary antibiotic discovery and stewardship efforts.202540627029
980880.9839Understanding 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.202541148650
816290.9839Nanotechnology 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
9172100.9839These Are the Genes You're Looking For: Finding Host Resistance Genes. Humanity's ongoing struggle with new, re-emerging and endemic infectious diseases serves as a frequent reminder of the need to understand host-pathogen interactions. Recent advances in genomics have dramatically advanced our understanding of how genetics contributes to host resistance or susceptibility to bacterial infection. Here we discuss current trends in defining host-bacterial interactions at the genome-wide level, including screens that harness CRISPR/Cas9 genome editing, natural genetic variation, proteomics, and transcriptomics. We report on the merits, limitations, and findings of these innovative screens and discuss their complementary nature. Finally, we speculate on future innovation as we continue to progress through the postgenomic era and towards deeper mechanistic insight and clinical applications.202133004258
6665110.9838A One-Health Perspective of Antimicrobial Resistance (AMR): Human, Animals and Environmental Health. Antibiotics are essential for treating bacterial and fungal infections in plants, animals, and humans. Their widespread use in agriculture and the food industry has significantly enhanced animal health and productivity. However, extensive and often inappropriate antibiotic use has driven the emergence and spread of antimicrobial resistance (AMR), a global health crisis marked by the reduced efficacy of antimicrobial treatments. Recognized by the World Health Organization (WHO) as one of the top ten global public health threats, AMR arises when certain bacteria harbor antimicrobial resistance genes (ARGs) that confer resistance that can be horizontally transferred to other bacteria, accelerating resistance spread in the environment. AMR poses a significant global health challenge, affecting humans, animals, and the environment alike. A One-Health perspective highlights the interconnected nature of these domains, emphasizing that resistant microorganisms spread across healthcare, agriculture, and the environment. Recent scientific advances such as metagenomic sequencing for resistance surveillance, innovative wastewater treatment technologies (e.g., ozonation, UV, membrane filtration), and the development of vaccines and probiotics as alternatives to antibiotics in livestock are helping to mitigate resistance. At the policy level, global initiatives including the WHO Global Action Plan on AMR, coordinated efforts by (Food and Agriculture Organization) FAO and World Organisation for Animal Health (WOAH), and recommendations from the O'Neill Report underscore the urgent need for international collaboration and sustainable interventions. By integrating these scientific and policy responses within the One-Health framework, stakeholders can improve antibiotic stewardship, reduce environmental contamination, and safeguard effective treatments for the future.202541157271
9719120.9838Dynamics of antibiotic resistance genes in plasmids and bacteriophages. This brief review explores the intricate interplay between bacteriophages and plasmids in the context of antibiotic resistance gene (ARG) dissemination. Originating from studies in the late 1950s, the review traces the evolution of knowledge regarding extrachromosomal factors facilitating horizontal gene transfer and adaptation in bacteria. Analyzing the gene repertoires of plasmids and bacteriophages, the study highlights their contributions to bacterial evolution and adaptation. While plasmids encode essential and accessory genes influencing host characteristics, bacteriophages carry auxiliary metabolic genes (AMGs) that augment host metabolism. The debate on phages carrying ARGs is explored through a critical evaluation of various studies, revealing contrasting findings from researchers. Additionally, the review addresses the interplay between prophages and plasmids, underlining their similarities and divergences. Based on the available literature evidence, we conclude that plasmids generally encode ARGs while bacteriophages typically do not contain ARGs. But extra-chromosomaly present prophages with plasmid characteristics can encode and disseminate ARGs.202538651513
8166130.9838A 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/s12088-024-01384-6.202540655388
6655140.9837Futuristic Non-antibiotic Therapies to Combat Antibiotic Resistance: A Review. The looming problem of resistance to antibiotics in microorganisms is a global health concern. The drug-resistant microorganisms originating from anthropogenic sources and commercial livestock farming have posed serious environmental and health challenges. Antibiotic-resistant genes constituting the environmental "resistome" get transferred to human and veterinary pathogens. Hence, deciphering the origin, mechanism and extreme of transfer of these genetic factors into pathogens is extremely important to develop not only the therapeutic interventions to curtail the infections, but also the strategies to avert the menace of microbial drug-resistance. Clinicians, researchers and policymakers should jointly come up to develop the strategies to prevent superfluous exposure of pathogens to antibiotics in non-clinical settings. This article highlights the present scenario of increasing antimicrobial-resistance in pathogenic bacteria and the clinical importance of unconventional or non-antibiotic therapies to thwart the infectious pathogenic microorganisms.202133574807
9187150.9836Recent 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
6397160.9836Microplastics and antibiotic resistance genes as rising threats: Their interaction represents an urgent environmental concern. Microplastics (MPs) have been reported to be emerging contaminant of different environmental niches like air, soil, and water. When exposed to these environments, MPs interact with already existing antibiotics to create combined pollution that can harm organisms. MPs have garnered significant attention in academic circles due to their ability to adsorb antibiotics. This review article explores different dimensions of MPs, antibiotic resistance genes (ARGs), and the interplay between MPs, antibiotics, and antibiotic-resistant bacteria (ARB), emphasizing their interconnection with soil and water pollution. It also summarizes the mechanisms behind the interaction between antibiotics and MPs, detailing various physical and chemical interactions. Additionally, it outlines the pathways through which MPs and ARGs complexes spread, offering insights for future research and solutions to tackle compound pollution. The article concludes by providing targeted strategies to mitigate the environmental and public health risks posed by MP-associated ARG transmission, highlighting the need for integrated pollution control, advanced monitoring techniques, and stricter regulatory policies.202540756460
8172170.9836From 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
8157180.9836Autologous DNA mobilization and multiplication expedite natural products discovery from bacteria. The transmission of antibiotic-resistance genes, comprising mobilization and relocation events, orchestrates the dissemination of antimicrobial resistance. Inspired by this evolutionarily successful paradigm, we developed ACTIMOT, a CRISPR-Cas9-based approach to unlock the vast chemical diversity concealed within bacterial genomes. ACTIMOT enables the efficient mobilization and relocation of large DNA fragments from the chromosome to replicative plasmids within the same bacterial cell. ACTIMOT circumvents the limitations of traditional molecular cloning methods involving handling and replicating large pieces of genomic DNA. Using ACTIMOT, we mobilized and activated four cryptic biosynthetic gene clusters from Streptomyces, leading to the discovery of 39 compounds across four distinct classes. This work highlights the potential of ACTIMOT for accelerating the exploration of biosynthetic pathways and the discovery of natural products.202439666857
6537190.9835Antibiotic Abuse in Ornamental Fish: An Overlooked Reservoir for Antibiotic Resistance. Ornamental fish represent a significant aquaculture sector with notable economic value, yet their contribution to antibiotic residues and resistance remains underrecognized. This review synthesizes evidence on widespread and often unregulated antibiotic use-including tetracyclines and fluoroquinolones-in ornamental fish production, transportation, and retail, primarily targeting bacterial diseases such as aeromonosis and vibriosis. Pathogenic microorganisms including Edwardsiella, Flavobacterium, and Shewanella spp. cause diseases like hemorrhagic septicemia, fin rot, skin ulcers, and exophthalmia, impairing fish health and marketability. Prophylactic and therapeutic antibiotic applications elevate antibiotic residues in fish tissues and carriage water, thereby selecting for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). These resistant elements pose significant risks to fish health, human exposure via direct contact and bioaerosols, and environmental health through contamination pathways. We emphasize the urgent need for a holistic One Health approach, involving enhanced surveillance, stringent regulatory oversight, and adoption of alternative antimicrobial strategies, such as probiotics and advanced water treatments. Coordinated global actions are crucial to effectively mitigate antibiotic resistance within the ornamental fish industry, ensuring sustainable production, safeguarding public health, and protecting environmental integrity.202540284775