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816100.9733Integrative 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
908610.9718Emergence 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.201829746491
650620.9713Mitigating antimicrobial resistance through effective hospital wastewater management in low- and middle-income countries. Hospital wastewater (HWW) is a significant environmental and public health threat, containing high levels of pollutants such as antibiotic-resistant bacteria (ARB), antibiotic-resistant genes (ARGs), antibiotics, disinfectants, and heavy metals. This threat is of particular concern in low- and middle-income countries (LMICs), where untreated effluents are often used for irrigating vegetables crops, leading to direct and indirect human exposure. Despite being a potential hotspot for the spread of antimicrobial resistance (AMR), existing HWW treatment systems in LMICs primarily target conventional pollutants and lack effective standards for monitoring the removal of ARB and ARGs. Consequently, untreated or inadequately treated HWW continues to disseminate ARB and ARGs, exacerbating the risk of AMR proliferation. Addressing this requires targeted interventions, including cost-effective treatment solutions, robust AMR monitoring protocols, and policy-driven strategies tailored to LMICs. This perspective calls for a paradigm shift in HWW management in LMIC, emphasizing the broader implementation of onsite treatment systems, which are currently rare. Key recommendations include developing affordable and contextually adaptable technologies for eliminating ARB and ARGs and enforcing local regulations for AMR monitoring and control in wastewater. Addressing these challenges is essential for protecting public health, preventing the environmental spread of resistance, and contributing to a global effort to preserve the efficacy of antibiotics. Recommendations include integrating scalable onsite technologies, leveraging local knowledge, and implementing comprehensive AMR-focused regulatory frameworks.202439944563
843230.9712A 0D-2D Heterojunction Bismuth Molybdate-Anchored Multifunctional Hydrogel for Highly Efficient Eradication of Drug-Resistant Bacteria. Due to the increasing antibiotic resistance and the lack of broad-spectrum antibiotics, there is an urgent requirement to develop fresh strategies to combat multidrug-resistant pathogens. Herein, defect-rich bismuth molybdate heterojunctions [zero-dimensional (0D) Bi(4)MoO(9)/two-dimensional (2D) Bi(2)MoO(6), MBO] were designed for rapid capture of bacteria and synergistic photocatalytic sterilization. The as-prepared MBO was experimentally and theoretically demonstrated to possess defects, heterojunctions, and irradiation triple-enhanced photocatalytic activity for efficient generation of reactive oxygen species (ROS) due to the exposure of more active sites and separation of effective electron-hole pairs. Meanwhile, dopamine-modified MBO (pMBO) achieved a positively charged and rough surface, which conferred strong bacterial adhesion and physical penetration to the nanosheets, effectively trapping bacteria within the damage range and enhancing ROS damage. Based on this potent antibacterial ability of pMBO, a multifunctional hydrogel consisting of poly(vinyl alcohol) cross-linked tannic acid-coated cellulose nanocrystals (CPTB) and pMBO, namely CPTB@pMBO, is developed and convincingly effective against methicillin-resistant Staphylococcus aureus in a mouse skin infection model. In addition, the strategy of combining a failed beta-lactam antibiotic with CPTB@pMBO to photoinactivation with no resistance observed was developed, which presented an idea to address the issue of antibiotic resistance in bacteria and to explore facile anti-infection methods. In addition, CPTB@pMBO can reduce excessive proteolysis of tissue and inflammatory response by regulating the expression of genes and pro-inflammatory factors in vivo, holding great potential for the effective treatment of wound infections caused by drug-resistant bacteria.202337531599
843340.9710Thermoresponsive Nanostructures: From Mechano-Bactericidal Action to Bacteria Release. Overuse of antibiotics can increase the risk of notorious antibiotic resistance in bacteria, which has become a growing public health concern worldwide. Featured with the merit of mechanical rupture of bacterial cells, the bioinspired nanopillars are promising alternatives to antibiotics for combating bacterial infections while avoiding antibacterial resistance. However, the resident dead bacterial cells on nanopillars may greatly impair their bactericidal capability and ultimately impede their translational potential toward long-term applications. Here, we show that the functions of bactericidal nanopillars can be significantly broadened by developing a hybrid thermoresponsive polymer@nanopillar-structured surface, which retains all of the attributes of pristine nanopillars and adds one more: releasing dead bacteria. We fabricate this surface through coaxially decorating mechano-bactericidal ZnO nanopillars with thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes. Combining the benefits of ZnO nanopillars and PNIPAAm chains, the antibacterial performances can be controllably regulated between ultrarobust mechano-bactericidal action (∼99%) and remarkable bacteria-releasing efficiency (∼98%). Notably, both the mechanical sterilization against the live bacteria and the controllable release for the pinned dead bacteria solely stem from physical actions, stimulating the exploration of intelligent structure-based bactericidal surfaces with persistent antibacterial properties without the risk of triggering drug resistance.202134905683
907650.9710ResiDB: An automated database manager for sequence data. The amount of publicly available DNA sequence data is drastically increasing, making it a tedious task to create sequence databases necessary for the design of diagnostic assays. The selection of appropriate sequences is especially challenging in genes affected by frequent point mutations such as antibiotic resistance genes. To overcome this issue, we have designed the webtool resiDB, a rapid and user-friendly sequence database manager for bacteria, fungi, viruses, protozoa, invertebrates, plants, archaea, environmental and whole genome shotgun sequence data. It automatically identifies and curates sequence clusters to create custom sequence databases based on user-defined input sequences. A collection of helpful visualization tools gives the user the opportunity to easily access, evaluate, edit, and download the newly created database. Consequently, researchers do no longer have to manually manage sequence data retrieval, deal with hardware limitations, and run multiple independent software tools, each having its own requirements, input and output formats. Our tool was developed within the H2020 project FAPIC aiming to develop a single diagnostic assay targeting all sepsis-relevant pathogens and antibiotic resistance mechanisms. ResiDB is freely accessible to all users through https://residb.ait.ac.at/.202133495705
905060.9710Cationic Polysaccharide Conjugates as Antibiotic Adjuvants Resensitize Multidrug-Resistant Bacteria and Prevent Resistance. In recent years, traditional antibiotic efficacy has rapidly diminished due to the advent of multidrug-resistant (MDR) bacteria, which poses severe threat to human life and globalized healthcare. Currently, the development cycle of new antibiotics cannot match the ongoing MDR infection crisis. Therefore, novel strategies are required to resensitize MDR bacteria to existing antibiotics. In this study, novel cationic polysaccharide conjugates Dextran-graft-poly(5-(1,2-dithiolan-3-yl)-N-(2-guanidinoethyl)pentanamide) (Dex-g-PSS(n) ) is synthesized using disulfide exchange polymerization. Critically, bacterial membranes and efflux pumps are disrupted by a sub-inhibitory concentration of Dex-g-PSS(30) , which enhances rifampicin (RIF) accumulation inside bacteria and restores its efficacy. Combined Dex-g-PSS(30) and RIF prevents bacterial resistance in bacteria cultured over 30 generations. Furthermore, Dex-g-PSS(30) restores RIF effectiveness, reduces inflammatory reactions in a pneumonia-induced mouse model, and exhibits excellent in vivo biological absorption and degradation capabilities. As an antibiotic adjuvant, Dex-g-PSS(30) provides a novel resensitizing strategy for RIF against MDR bacteria and bacterial resistance. This Dex-g-PSS(30) research provides a solid platform for future MDR applications.202235962720
843770.9708Tocopherol polyethylene glycol succinate-modified hollow silver nanoparticles for combating bacteria-resistance. Multiple drug resistance and the increase in the appearance of superbugs together with the exceedingly scant development of new potent antibiotic drugs pose an urgent global medical threat and imminent public security crisis. In the present study, we fabricated well-dispersed tocopherol polyethylene glycol succinate (TPGS)-capped silver nanoparticles (AgNPs) of about 10 nm in size. The hollow structure of the TPGS-capped AgNPs (TPGS/AgNPs) was confirmed and applied to load antibiotics. The TPGS/AgNPs proved to be able to cross the bacterial cell wall and penetrate into bacteria, thereby delivering more of the antibiotic to the interior of bacteria and thus enhancing the in vitro antibacterial effect of the antibiotic, even overcoming the drug-resistance in drug-resistant E. coli and Acinetobacter baumannii. It was found that the TPGS modification in the TPGS/AgNPs could decrease the activity of the efflux pumps AdeABC and AdeIJK in drug-resistant Acinetobacter baumannii via inhibiting the efflux pump genes adeB and adeJ, thus increasing the accumulation of the delivered antibiotic and overcoming the drug-resistance. Tigecycline delivered by TPGS/AgNPs could effectively antagonize drug-resistance in an acute peritonitis model mice, thereby increasing the survival rate and alleviating the inflammatory response. TPGS/AgNPs were developed as a novel and effective antibiotic delivery system and TPGS was demonstrated to have great potential as a pharmaceutical excipient for use in drug-resistant infection therapy.201930968093
843680.9707NIR-Activated Hydrogel with Dual-Enhanced Antibiotic Effectiveness for Thorough Elimination of Antibiotic-Resistant Bacteria. Antibiotic resistance has become a critical health crisis globally. Traditional strategies using antibiotics can lead to drug-resistance, while inorganic antimicrobial agents can cause severe systemic toxicity. Here, we have developed a dual-antibiotic hydrogel delivery system (PDA-Ag@Levo/CMCS), which can achieve controlled release of clinical antibiotics levofloxacin (Levo) and classic nanoscale antibiotic silver nanoparticles (AgNPs), effectively eliminating drug-resistant P. aeruginosa. Benefiting from the photothermal (PTT) effect of polydopamine (PDA), the local high temperature generated by PDA-Ag@Levo/CMCS can quickly kill bacteria through continuous and responsive release of dual-antibiotics to restore sensitivity to ineffective antibiotics. Moreover, AgNPs could significantly improve the efficiency of traditional antibiotics by disrupting bacterial membranes and reducing their toxicity to healthy tissues. A clever combination of PTT and drug-combination therapy can effectively eliminate biofilms and drug-resistant bacteria. Mechanism studies have shown that PDA-Ag@Levo might eliminate drug-resistant P. aeruginosa by disrupting biofilm formation and protein synthesis, and inhibit the resistance mutation of P. aeruginosa by promoting the expression of related genes, such as rpoS, dinB, and mutS. Collectively, the synergistic effect of this dual-antibiotic hydrogel combined with PTT provides a creative strategy for eliminating drug-resistant bacteria in chronic infection wounds.202539760335
855390.9707Unveiling the power of nanotechnology: a novel approach to eliminating antibiotic-resistant bacteria and genes from municipal effluent. The increasing global population and declining freshwater resources have heightened the urgency of ensuring safe and accessible water supplies.Query The persistence of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in municipal effluents poses a significant public health threat, exacerbated by the widespread use of antibiotics and the inadequate removal of contaminants in wastewater treatment facilities. Conventional treatment methods often fail to eliminate these emerging pollutants, facilitating their entry into agricultural systems and natural water bodies, thereby accelerating the spread of antimicrobial resistance. To address these challenges, interdisciplinary strategies in water treatment are essential. Nanotechnology has emerged as a promising approach due to its unique physicochemical properties, biocompatibility, and high efficiency in detecting and removing biological and chemical contaminants. Various nanomaterials, including graphene-based structures, Carbon nanotubes (CNTs), noble metal nanoparticles (gold (Au) and silver (Ag)), silicon and chitosan-based nanomaterials, as well as titanium and Zinc oxide (ZnO) nanomaterials, demonstrate potent antimicrobial effects. Moreover, nanosensors and photocatalysts utilizing these nanomaterials enable precise detection and effective degradation of ARB and ARGs in wastewater. This review examines the mechanisms by which nanotechnology-based materials can mitigate the risks associated with antibiotic resistance in urban effluents, focusing on their applications in pathogen detection, pollutant removal, and wastewater treatment. By integrating nanotechnology into existing treatment frameworks, we can significantly enhance the efficiency of water purification processes, ultimately contributing to global water security and the protection of public health.202540512401
6664100.9706Addressing the global challenge of bacterial drug resistance: insights, strategies, and future directions. The COVID-19 pandemic underscored bacterial resistance as a critical global health issue, exacerbated by the increased use of antibiotics during the crisis. Notwithstanding the pandemic's prevalence, initiatives to address bacterial medication resistance have been inadequate. Although an overall drop in worldwide antibiotic consumption, total usage remains substantial, requiring rigorous regulatory measures and preventive activities to mitigate the emergence of resistance. Although National Action Plans (NAPs) have been implemented worldwide, significant disparities persist, particularly in low- and middle-income countries (LMICs). Settings such as farms, hospitals, wastewater treatment facilities, and agricultural environments include a significant presence of Antibiotic Resistant Bacteria (ARB) and antibiotic-resistance genes (ARG), promoting the propagation of resistance. Dietary modifications and probiotic supplementation have shown potential in reshaping gut microbiota and reducing antibiotic resistance gene prevalence. Combining antibiotics with adjuvants or bacteriophages may enhance treatment efficacy and mitigate resistance development. Novel therapeutic approaches, such as tailored antibiotics, monoclonal antibodies, vaccines, and nanoparticles, offer alternate ways of addressing resistance. In spite of advancements in next-generation sequencing and analytics, gaps persist in comprehending the role of gut microbiota in regulating antibiotic resistance. Effectively tackling antibiotic resistance requires robust policy interventions and regulatory measures targeting root causes while minimizing public health risks. This review provides information for developing strategies and protocols to prevent bacterial colonization, enhance gut microbiome resilience, and mitigate the spread of antibiotic resistance.202540066274
8554110.9706Nanomaterial-Enhanced Hybrid Disinfection: A Solution to Combat Multidrug-Resistant Bacteria and Antibiotic Resistance Genes in Wastewater. This review explores the potential of nanomaterial-enhanced hybrid disinfection methods as effective strategies for addressing the growing challenge of multidrug-resistant (MDR) bacteria and antibiotic resistance genes (ARGs) in wastewater treatment. By integrating hybrid nanocomposites and nanomaterials, natural biocides such as terpenes, and ultrasonication, this approach significantly enhances disinfection efficiency compared to conventional methods. The review highlights the mechanisms through which hybrid nanocomposites and nanomaterials generate reactive oxygen species (ROS) under blue LED irradiation, effectively disrupting MDR bacteria while improving the efficacy of natural biocides through synergistic interactions. Additionally, the review examines critical operational parameters-such as light intensity, catalyst dosage, and ultrasonication power-that optimize treatment outcomes and ensure the reusability of hybrid nanocomposites and other nanomaterials without significant loss of photocatalytic activity. Furthermore, this hybrid method shows promise in degrading ARGs, thereby addressing both microbial and genetic pollution. Overall, this review underscores the need for innovative wastewater treatment solutions that are efficient, sustainable, and scalable, contributing to the global fight against antimicrobial resistance.202439591087
6508120.9706Synergizing 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
9192130.9705Antimicrobial peptides: Sustainable application informed by evolutionary constraints. The proliferation and global expansion of multidrug-resistant (MDR) bacteria have deepened the need to develop novel antimicrobials. Antimicrobial peptides (AMPs) are regarded as promising antibacterial agents because of their broad-spectrum antibacterial activity and multifaceted mechanisms of action with non-specific targets. However, if AMPs are to be applied sustainably, knowledge of how they induce resistance in pathogenic bacteria must be mastered to avoid repeating the traditional antibiotic resistance mistakes currently faced. Furthermore, the evolutionary constraints on the acquisition of AMP resistance by microorganisms in the natural environment, such as functional compatibility and fitness trade-offs, inform the translational application of AMPs. Consequently, the shortcut to achieve sustainable utilization of AMPs is to uncover the evolutionary constraints of bacteria on AMP resistance in nature and find the tricks to exploit these constraints, such as applying AMP cocktails to minimize the efficacy of selection for resistance or combining nanomaterials to maximize the costs of AMP resistance. Altogether, this review dissects the benefits, challenges, and opportunities of utilizing AMPs against disease-causing bacteria, and highlights the use of AMP cocktails or nanomaterials to proactively address potential AMP resistance crises in the future.202235752270
6507140.9705What 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
8171150.9705Advancements 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
6648160.9705Multi-Drug Resistant Coliform: Water Sanitary Standards and Health Hazards. Water constitutes and sustains life; however, its pollution afflicts its necessity, further worsening its scarcity. Coliform is one of the largest groups of bacteria evident in fecally polluted water, a major public health concern. Coliform thrive as commensals in the gut of warm-blooded animals, and are indefinitely passed through their feces into the environment. They are also called as model organisms as their presence is indicative of the prevalence of other potential pathogens, thus coliform are and unanimously employed as adept indicators of fecal pollution. As only a limited accessible source of fresh water is available on the planet, its contamination severely affects its usability. Coliform densities vary geographically and seasonally which leads to the lack of universally uniform regulatory guidelines regarding water potability often leads to ineffective detection of these model organisms and the misinterpretation of water quality status. Remedial measures such as disinfection, reducing the nutrient concentration or re-population doesn't hold context in huge lotic ecosystems such as freshwater rivers. There is also an escalating concern regarding the prevalence of multi-drug resistance in coliforms which renders antibiotic therapy incompetent. Antimicrobials are increasingly used in household, clinical, veterinary, animal husbandry and agricultural settings. Sub-optimal concentrations of these antimicrobials are unintentionally but regularly dispensed into the environment through seepages, sewages or runoffs from clinical or agricultural settings substantially adding to the ever-increasing pool of antibiotic resistance genes. When present below their minimum inhibitory concentration (MIC), these antimicrobials trigger the transfer of antibiotic-resistant genes that the coliform readily assimilate and further propagate to pathogens, the severity of which is evidenced by the high Multiple Antibiotic Resistance (MAR) index shown by the bacterial isolates procured from the environmental. This review attempts to assiduously anthologize the use of coliforms as water quality standards, their existent methods of detection and the issue of arising multi-drug resistance in them.201829946253
6649170.9705 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.200232687288
8173180.9704Advancing 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.202540990280
9083190.9704ARGNet: using deep neural networks for robust identification and classification of antibiotic resistance genes from sequences. BACKGROUND: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing. RESULTS: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG. CONCLUSIONS: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract.202438725076