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919200.9866Antimicrobial 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
908610.9866Emergence 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
861620.9864Mechanisms of inhibition and recovery under multi-antibiotic stress in anammox: A critical review. With the escalating global concern for emerging pollutants, particularly antibiotics, microplastics, and nanomaterials, the potential disruption they pose to critical environmental processes like anaerobic ammonia oxidation (anammox) has become a pressing issue. The anammox process, which plays a crucial role in nitrogen removal from wastewater, is particularly sensitive to external pollutants. This paper endeavors to address this knowledge gap by providing a comprehensive overview of the inhibition mechanisms of multi-antibiotic on anaerobic ammonia-oxidizing bacteria, along with insights into their recovery processes. The paper dives deeply into the various ways antibiotics interact with anammox bacteria, focusing specifically on their interference with the bacteria's extracellular polymers (EPS) - crucial components that maintain the structural integrity and functionality of the cells. Additionally, it explores how anammox bacteria utilize quorum sensing (QS) mechanisms to regulate their community structure and respond to antibiotic stress. Moreover, the paper summarizes effective removal methods for these antibiotics from wastewater systems, which is crucial for mitigating their inhibitory effects on anammox bacteria. Finally, the paper offers valuable insights into how anammox communities can recuperate from multi-antibiotic stress. This includes strategies for reintroducing healthy bacteria, optimizing operational conditions, and using bioaugmentation techniques to enhance the resilience of anammox communities. In summary, this paper not only enriches our understanding of the complex interactions between antibiotics and anammox bacteria but also provides theoretical and practical guidance for the treatment of antibiotic pollution in sewage, ensuring the sustainability and effectiveness of wastewater treatment processes.202439366232
840030.9863Transferring knowledge of bacterial protein interaction networks to predict pathogen targeted human genes and immune signaling pathways: a case study on M. tuberculosis. BACKGROUND: Bacterial invasive infection and host immune response is fundamental to the understanding of pathogen pathogenesis and the discovery of effective therapeutic drugs. However, there are very few experimental studies on the signaling cross-talks between bacteria and human host to date. METHODS: In this work, taking M. tuberculosis H37Rv (MTB) that is co-evolving with its human host as an example, we propose a general computational framework that exploits the known bacterial pathogen protein interaction networks in STRING database to predict pathogen-host protein interactions and their signaling cross-talks. In this framework, significant interlogs are derived from the known pathogen protein interaction networks to train a predictive l(2)-regularized logistic regression model. RESULTS: The computational results show that the proposed method achieves excellent performance of cross validation as well as low predicted positive rates on the less significant interlogs and non-interlogs, indicating a low risk of false discovery. We further conduct gene ontology (GO) and pathway enrichment analyses of the predicted pathogen-host protein interaction networks, which potentially provides insights into the machinery that M. tuberculosis H37Rv targets human genes and signaling pathways. In addition, we analyse the pathogen-host protein interactions related to drug resistance, inhibition of which potentially provides an alternative solution to M. tuberculosis H37Rv drug resistance. CONCLUSIONS: The proposed machine learning framework has been verified effective for predicting bacteria-host protein interactions via known bacterial protein interaction networks. For a vast majority of bacterial pathogens that lacks experimental studies of bacteria-host protein interactions, this framework is supposed to achieve a general-purpose applicability. The predicted protein interaction networks between M. tuberculosis H37Rv and Homo sapiens, provided in the Additional files, promise to gain applications in the two fields: (1) providing an alternative solution to drug resistance; (2) revealing the patterns that M. tuberculosis H37Rv genes target human immune signaling pathways.201829954330
825940.9862Secondary Metabolite Transcriptomic Pipeline (SeMa-Trap), an expression-based exploration tool for increased secondary metabolite production in bacteria. For decades, natural products have been used as a primary resource in drug discovery pipelines to find new antibiotics, which are mainly produced as secondary metabolites by bacteria. The biosynthesis of these compounds is encoded in co-localized genes termed biosynthetic gene clusters (BGCs). However, BGCs are often not expressed under laboratory conditions. Several genetic manipulation strategies have been developed in order to activate or overexpress silent BGCs. Significant increases in production levels of secondary metabolites were indeed achieved by modifying the expression of genes encoding regulators and transporters, as well as genes involved in resistance or precursor biosynthesis. However, the abundance of genes encoding such functions within bacterial genomes requires prioritization of the most promising ones for genetic manipulation strategies. Here, we introduce the 'Secondary Metabolite Transcriptomic Pipeline' (SeMa-Trap), a user-friendly web-server, available at https://sema-trap.ziemertlab.com. SeMa-Trap facilitates RNA-Seq based transcriptome analyses, finds co-expression patterns between certain genes and BGCs of interest, and helps optimize the design of comparative transcriptomic analyses. Finally, SeMa-Trap provides interactive result pages for each BGC, allowing the easy exploration and comparison of expression patterns. In summary, SeMa-Trap allows a straightforward prioritization of genes that could be targeted via genetic engineering approaches to (over)express BGCs of interest.202235580059
918250.9861Harnessing CRISPR/Cas9 in engineering biotic stress immunity in crops. There is significant potential for CRISPR/Cas9 to be used in developing crops that can adapt to biotic stresses such as fungal, bacterial, viral, and pest infections and weeds. The increasing global population and climate change present significant threats to food security by putting stress on plants, making them more vulnerable to diseases and productivity losses caused by pathogens, pests, and weeds. Traditional breeding methods are inadequate for the rapid development of new plant traits needed to counteract this decline in productivity. However, modern advances in genome-editing technologies, particularly CRISPR/Cas9, have transformed crop protection through precise and targeted modifications of plant genomes. This enables the creation of resilient crops with improved resistance to pathogens, pests, and weeds. This review examines various methods by which CRISPR/Cas9 can be utilized for crop protection. These methods include knocking out susceptibility genes, introducing resistance genes, and modulating defense genes. Potential applications of CRISPR/Cas9 in crop protection involve introducing genes that confer resistance to pathogens, disrupting insect genes responsible for survival and reproduction, and engineering crops that are resistant to herbicides. In conclusion, CRISPR/Cas9 holds great promise for advancing crop protection and ensuring food security in the face of environmental challenges and increasing population pressures. The most recent advancements in CRISPR technology for creating resistance to bacteria, fungi, viruses, and pests are covered here. We wrap up by outlining the most pressing issues and technological shortcomings, as well as unanswered questions for further study.202540663257
817160.9860Advancements 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
919170.9860Blunted blades: new CRISPR-derived technologies to dissect microbial multi-drug resistance and biofilm formation. The spread of multi-drug-resistant (MDR) pathogens has rapidly outpaced the development of effective treatments. Diverse resistance mechanisms further limit the effectiveness of our best treatments, including multi-drug regimens and last line-of-defense antimicrobials. Biofilm formation is a powerful component of microbial pathogenesis, providing a scaffold for efficient colonization and shielding against anti-microbials, which further complicates drug resistance studies. Early genetic knockout tools didn't allow the study of essential genes, but clustered regularly interspaced palindromic repeat inference (CRISPRi) technologies have overcome this challenge via genetic silencing. These tools rapidly evolved to meet new demands and exploit native CRISPR systems. Modern tools range from the creation of massive CRISPRi libraries to tunable modulation of gene expression with CRISPR activation (CRISPRa). This review discusses the rapid expansion of CRISPRi/a-based technologies, their use in investigating MDR and biofilm formation, and how this drives further development of a potent tool to comprehensively examine multi-drug resistance.202438511958
917980.9859A detailed landscape of CRISPR-Cas-mediated plant disease and pest management. Genome editing technology has rapidly evolved to knock-out genes, create targeted genetic variation, install precise insertion/deletion and single nucleotide changes, and perform large-scale alteration. The flexible and multipurpose editing technologies have started playing a substantial role in the field of plant disease management. CRISPR-Cas has reduced many limitations of earlier technologies and emerged as a versatile toolbox for genome manipulation. This review summarizes the phenomenal progress of the use of the CRISPR toolkit in the field of plant pathology. CRISPR-Cas toolbox aids in the basic studies on host-pathogen interaction, in identifying virulence genes in pathogens, deciphering resistance and susceptibility factors in host plants, and engineering host genome for developing resistance. We extensively reviewed the successful genome editing applications for host plant resistance against a wide range of biotic factors, including viruses, fungi, oomycetes, bacteria, nematodes, insect pests, and parasitic plants. Recent use of CRISPR-Cas gene drive to suppress the population of pathogens and pests has also been discussed. Furthermore, we highlight exciting new uses of the CRISPR-Cas system as diagnostic tools, which rapidly detect pathogenic microorganism. This comprehensive yet concise review discusses innumerable strategies to reduce the burden of crop protection.202235835393
816190.9859Integrative 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
8288100.9859Metabolic pathways and antimicrobial peptide resistance in bacteria. Antimicrobial resistance is a pressing concern that poses a significant threat to global public health, necessitating the exploration of alternative strategies to combat drug-resistant microbial infections. Recently, antimicrobial peptides (AMPs) have gained substantial attention as possible replacements for conventional antibiotics. Because of their pharmacodynamics and killing mechanisms, AMPs display a lower risk of bacterial resistance evolution compared with most conventional antibiotics. However, bacteria display different mechanisms to resist AMPs, and the role of metabolic pathways in the resistance mechanism is not fully understood. This review examines the intricate relationship between metabolic genes and AMP resistance, focusing on the impact of metabolic pathways on various aspects of resistance. Metabolic pathways related to guanosine pentaphosphate (pppGpp) and guanosine tetraphosphate (ppGpp) [collectively (p)ppGpp], the tricarboxylic acid (TCA) cycle, haem biosynthesis, purine and pyrimidine biosynthesis, and amino acid and lipid metabolism influence in different ways metabolic adjustments, biofilm formation and energy production that could be involved in AMP resistance. By targeting metabolic pathways and their associated genes, it could be possible to enhance the efficacy of existing antimicrobial therapies and overcome the challenges exhibited by phenotypic (recalcitrance) and genetic resistance toward AMPs. Further research in this area is needed to provide valuable insights into specific mechanisms, uncover novel therapeutic targets, and aid in the fight against antimicrobial resistance.202438742645
9186110.9859From Gene Editing to Biofilm Busting: CRISPR-CAS9 Against Antibiotic Resistance-A Review. In recent decades, the development of novel antimicrobials has significantly slowed due to the emergence of antimicrobial resistance (AMR), intensifying the global struggle against infectious diseases. Microbial populations worldwide rapidly develop resistance due to the widespread use of antibiotics, primarily targeting drug-resistant germs. A prominent manifestation of this resistance is the formation of biofilms, where bacteria create protective layers using signaling pathways such as quorum sensing. In response to this challenge, the CRISPR-Cas9 method has emerged as a ground-breaking strategy to counter biofilms. Initially identified as the "adaptive immune system" of bacteria, CRISPR-Cas9 has evolved into a state-of-the-art genetic engineering tool. Its exceptional precision in altering specific genes across diverse microorganisms positions it as a promising alternative for addressing antibiotic resistance by selectively modifying genes in diverse microorganisms. This comprehensive review concentrates on the historical background, discovery, developmental stages, and distinct components of CRISPR Cas9 technology. Emphasizing its role as a widely used genome engineering tool, the review explores how CRISPR Cas9 can significantly contribute to the targeted disruption of genes responsible for biofilm formation, highlighting its pivotal role in reshaping strategies to combat antibiotic resistance and mitigate the challenges posed by biofilm-associated infectious diseases.202438702575
9172120.9858These 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
8403130.9858Uncovering virulence factors in Cronobacter sakazakii: insights from genetic screening and proteomic profiling. The increasing problem of antibiotic resistance has driven the search for virulence factors in pathogenic bacteria, which can serve as targets for the development of new antibiotics. Although whole-genome Tn5 transposon mutagenesis combined with phenotypic assays has been a widely used approach, its efficiency remains low due to labor-intensive processes. In this study, we aimed to identify specific genes and proteins associated with the virulence of Cronobacter sakazakii, a pathogenic bacterium known for causing severe infections, particularly in infants and immunocompromised individuals. By employing a combination of genetic screening, comparative proteomics, and in vivo validation using zebrafish and rat models, we rapidly screened highly virulent strains and identified two genes, rcsA and treR, as potential regulators of C. sakazakii toxicity toward zebrafish and rats. Proteomic profiling revealed upregulated proteins upon knockout of rcsA and treR, including FabH, GshA, GppA, GcvH, IhfB, RfaC, MsyB, and three unknown proteins. Knockout of their genes significantly weakened bacterial virulence, confirming their role as potential virulence factors. Our findings contribute to understanding the pathogenicity of C. sakazakii and provide insights into the development of targeted interventions and therapies against this bacterium.IMPORTANCEThe emergence of antibiotic resistance in pathogenic bacteria has become a critical global health concern, necessitating the identification of virulence factors as potential targets for the development of new antibiotics. This study addresses the limitations of conventional approaches by employing a combination of genetic screening, comparative proteomics, and in vivo validation to rapidly identify specific genes and proteins associated with the virulence of Cronobacter sakazakii, a highly pathogenic bacterium responsible for severe infections in vulnerable populations. The identification of two genes, rcsA and treR, as potential regulators of C. sakazakii toxicity toward zebrafish and rats and the proteomic profiling upon knockout of rcsA and treR provides novel insights into the mechanisms underlying bacterial virulence. The findings contribute to our understanding of C. sakazakii's pathogenicity, shed light on the regulatory pathways involved in bacterial virulence, and offer potential targets for the development of novel interventions against this highly virulent bacterium.202337750707
9216140.9857Mitigating Antibiotic Resistance: The Utilization of CRISPR Technology in Detection. Antibiotics, celebrated as some of the most significant pharmaceutical breakthroughs in medical history, are capable of eliminating or inhibiting bacterial growth, offering a primary defense against a wide array of bacterial infections. However, the rise in antimicrobial resistance (AMR), driven by the widespread use of antibiotics, has evolved into a widespread and ominous threat to global public health. Thus, the creation of efficient methods for detecting resistance genes and antibiotics is imperative for ensuring food safety and safeguarding human health. The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) systems, initially recognized as an adaptive immune defense mechanism in bacteria and archaea, have unveiled their profound potential in sensor detection, transcending their notable gene-editing applications. CRISPR/Cas technology employs Cas enzymes and guides RNA to selectively target and cleave specific DNA or RNA sequences. This review offers an extensive examination of CRISPR/Cas systems, highlighting their unique attributes and applications in antibiotic detection. It outlines the current utilization and progress of the CRISPR/Cas toolkit for identifying both nucleic acid (resistance genes) and non-nucleic acid (antibiotic micromolecules) targets within the field of antibiotic detection. In addition, it examines the current challenges, such as sensitivity and specificity, and future opportunities, including the development of point-of-care diagnostics, providing strategic insights to facilitate the curbing and oversight of antibiotic-resistance proliferation.202439727898
8178150.9857Unraveling 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
9115160.9857RND Efflux Pump Induction: A Crucial Network Unveiling Adaptive Antibiotic Resistance Mechanisms of Gram-Negative Bacteria. The rise of multi-drug-resistant (MDR) pathogenic bacteria presents a grave challenge to global public health, with antimicrobial resistance ranking as the third leading cause of mortality worldwide. Understanding the mechanisms underlying antibiotic resistance is crucial for developing effective treatments. Efflux pumps, particularly those of the resistance-nodulation-cell division (RND) superfamily, play a significant role in expelling molecules from bacterial cells, contributing to the emergence of multi-drug resistance. These are transmembrane transporters naturally produced by Gram-negative bacteria. This review provides comprehensive insights into the modulation of RND efflux pump expression in bacterial pathogens by numerous and common molecules (bile, biocides, pharmaceuticals, additives, plant extracts, etc.). The interplay between these molecules and efflux pump regulators underscores the complexity of antibiotic resistance mechanisms. The clinical implications of efflux pump induction by non-antibiotic compounds highlight the challenges posed to public health and the urgent need for further investigation. By addressing antibiotic resistance from multiple angles, we can mitigate its impact and preserve the efficacy of antimicrobial therapies.202438927168
6647170.9857Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods. Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the "gut resistome." ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.202032117102
6397180.9857Microplastics 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
6442190.9857A systematic review of antibiotic resistance driven by metal-based nanoparticles: Mechanisms and a call for risk mitigation. Elevations in antibiotic resistance genes (ARGs) are due not only to the antibiotic burden, but also to numerous environmental pressures (e.g., pesticides, metal ions, or psychotropic pharmaceuticals), which have led to an international public health emergency. Metal-based nanoparticles (MNPs) poison bacteria while propelling nanoresistance at ambient or sub-lethal concentrations, acting as a wide spectrum germicidal agent. Awareness of MNPs driven antibiotic resistance has created a surge of investigation into the molecule mechanisms of evolving and spreading environmental antibiotic resistome. Co-occurrence of MNPs resistance and antibiotic resistance emerge in environmental pathogens and benign microbes may entail a crucial outcome for human health. In this review we expound on the systematic mechanism of ARGs proliferation under the stress of MNPs, including reactive oxygen species (ROS) induced mutation, horizontal gene transfer (HGT) relevant genes regulation, nano-property, quorum sensing, and biofilm formation and highlighting on the momentous contribution of nanoparticle released ion. As antibiotic resistance pattern alteration is closely knit with the mediate activation of nanoparticle in water, soil, manure, or sludge habitats, we have proposed a virulence and evolution based antibiotic resistance risk assessment strategy for MNP contaminated areas and discussed practicable approaches that call for risk management in critical environmental compartments.202438220012