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907600.9939ResiDB: 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
907710.9935The PLSDB 2025 update: enhanced annotations and improved functionality for comprehensive plasmid research. Plasmids are extrachromosomal DNA molecules in bacteria and archaea, playing critical roles in horizontal gene transfer, antibiotic resistance, and pathogenicity. Since its first release in 2018, our database on plasmids, PLSDB, has significantly grown and enhanced its content and scope. From 34 513 records contained in the 2021 version, PLSDB now hosts 72 360 entries. Designed to provide life scientists with convenient access to extensive plasmid data and to support computer scientists by offering curated datasets for artificial intelligence (AI) development, this latest update brings more comprehensive and accurate information for plasmid research, with interactive visualization options. We enriched PLSDB by refining the identification and classification of plasmid host ecosystems and host diseases. Additionally, we incorporated annotations for new functional structures, including protein-coding genes and biosynthetic gene clusters. Further, we enhanced existing annotations, such as antimicrobial resistance genes and mobility typing. To accommodate these improvements and to host the increase plasmid sets, the webserver architecture and underlying data structures of PLSDB have been re-reconstructed, resulting in decreased response times and enhanced visualization of features while ensuring that users have access to a more efficient and user-friendly interface. The latest release of PLSDB is freely accessible at https://www.ccb.uni-saarland.de/plsdb2025.202539565221
816420.9935Antibiotic Resistance - A Cause for Reemergence of Infections. This article can rightly be called 'the rise of the microbial phoenix'; for, all the microbial infections whose doomsday was predicted with the discovery of antibiotics, have thumbed their noses at mankind and reemerged phoenix like. The hubris generated by Sir Alexander Fleming's discovery of Penicillin in 1928, exemplified best by the comment by William H Stewart, the US Surgeon General in 1967, "It is time to close the books on infectious diseases" has been replaced by the realisation that the threat of antibiotic resistance is, in the words of the Chief Medical Officer of England, Dame Sally Davies, "just as important and deadly as climate change and international terrorism". Antimicrobial resistance threatens to negate all the major medical advances of the last century because antimicrobial use is linked to many other fields like organ transplantation and cancer chemotherapy. Antibiotic resistance genes have been there since ancient times in response to naturally occurring antibiotics. Modern medicine has only driven further evolution of antimicrobial resistance by use, misuse, overuse and abuse of antibiotics. Resistant bacteria proliferate by natural selection when their drug sensitive comrades are removed by antibiotics. In this article the authors discuss the various causes of antimicrobial resistance and dwell in some detail on antibiotic resistance in gram-positive and gram-negative organisms. Finally they stress on the important role clinicians have in limiting the development and spread of antimicrobial resistance.202032026301
817130.9933Advancements 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
918440.9933Unlocking the potential of phages: Innovative approaches to harnessing bacteriophages as diagnostic tools for human diseases. Phages, viruses that infect bacteria, have been explored as promising tools for the detection of human disease. By leveraging the specificity of phages for their bacterial hosts, phage-based diagnostic tools can rapidly and accurately detect bacterial infections in clinical samples. In recent years, advances in genetic engineering and biotechnology have enabled the development of more sophisticated phage-based diagnostic tools, including those that express reporter genes or enzymes, or target specific virulence factors or antibiotic resistance genes. However, despite these advancements, there are still challenges and limitations to the use of phage-based diagnostic tools, including concerns over phage safety and efficacy. This review aims to provide a comprehensive overview of the current state of phage-based diagnostic tools, including their advantages, limitations, and potential for future development. By addressing these issues, we hope to contribute to the ongoing efforts to develop safe and effective phage-based diagnostic tools for the detection of human disease.202337770168
816150.9933Integrative 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
907560.9932CamPype: an open-source workflow for automated bacterial whole-genome sequencing analysis focused on Campylobacter. BACKGROUND: The rapid expansion of Whole-Genome Sequencing has revolutionized the fields of clinical and food microbiology. However, its implementation as a routine laboratory technique remains challenging due to the growth of data at a faster rate than can be effectively analyzed and critical gaps in bioinformatics knowledge. RESULTS: To address both issues, CamPype was developed as a new bioinformatics workflow for the genomics analysis of sequencing data of bacteria, especially Campylobacter, which is the main cause of gastroenteritis worldwide making a negative impact on the economy of the public health systems. CamPype allows fully customization of stages to run and tools to use, including read quality control filtering, read contamination, reads extension and assembly, bacterial typing, genome annotation, searching for antibiotic resistance genes, virulence genes and plasmids, pangenome construction and identification of nucleotide variants. All results are processed and resumed in an interactive HTML report for best data visualization and interpretation. CONCLUSIONS: The minimal user intervention of CamPype makes of this workflow an attractive resource for microbiology laboratories with no expertise in bioinformatics as a first line method for bacterial typing and epidemiological analyses, that would help to reduce the costs of disease outbreaks, or for comparative genomic analyses. CamPype is publicly available at https://github.com/JoseBarbero/CamPype .202337474912
980870.9931Understanding 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
955680.9931Recent 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
956190.9931The resistance tsunami, antimicrobial stewardship, and the golden age of microbiology. Modern medicine is built on antibiotics. Antibiotics are something that we take for granted. We have however spent over 60 years educating bacteria to become resistant, and the global resistance tsunami has caught everyone unawares. Since bacteria have changed, we also have to change, and to change most of the practices of how we use antibiotics. Because the development of new antibiotics is so expensive, a stewardship approach may help to preserve those that we have now while we work to develop new antibiotics and to develop other approaches to controlling and treating infections. We need to adopt the ethic of Good Stewardship Practice (GSP) as an active and dynamic process of continuous improvement in antibiotic use, a process with many steps of different sizes involving everyone involved in antibiotic use. All antibiotic users have an important role to play in GSP. Although the resistance situation is pessimistic, and the future of antibiotics looks uncertain, we are fortunately entering what may be seen as the golden age of microbiology. This encompasses an astonishing array of technologies for rapid pathogen and resistance gene detection, for clone identification by genome sequencing, for identification of novel bacterial genes and for identification of the Achilles' heels of different pathogens. Future antibiotics may have to be far more targeted to the individual pathogen and the site of infection. A global tax on antibiotics might reduce their use while funding the cost of developing new antibiotics and new approaches to control of infectious diseases.201424646601
8398100.9931ARTS 2.0: feature updates and expansion of the Antibiotic Resistant Target Seeker for comparative genome mining. Multi-drug resistant pathogens have become a major threat to human health and new antibiotics are urgently needed. Most antibiotics are derived from secondary metabolites produced by bacteria. In order to avoid suicide, these bacteria usually encode resistance genes, in some cases within the biosynthetic gene cluster (BGC) of the respective antibiotic compound. Modern genome mining tools enable researchers to computationally detect and predict BGCs that encode the biosynthesis of secondary metabolites. The major challenge now is the prioritization of the most promising BGCs encoding antibiotics with novel modes of action. A recently developed target-directed genome mining approach allows researchers to predict the mode of action of the encoded compound of an uncharacterized BGC based on the presence of resistant target genes. In 2017, we introduced the 'Antibiotic Resistant Target Seeker' (ARTS). ARTS allows for specific and efficient genome mining for antibiotics with interesting and novel targets by rapidly linking housekeeping and known resistance genes to BGC proximity, duplication and horizontal gene transfer (HGT) events. Here, we present ARTS 2.0 available at http://arts.ziemertlab.com. ARTS 2.0 now includes options for automated target directed genome mining in all bacterial taxa as well as metagenomic data. Furthermore, it enables comparison of similar BGCs from different genomes and their putative resistance genes.202032427317
8168110.9931Understanding antimicrobial resistance (AMR) mechanisms and advancements in AMR diagnostics. The overuse and abuse of antibiotics, which results in the evolution of resistant microorganisms, is the primary cause of the global health catastrophe known as antimicrobial resistance (AMR). The enzymatic breakdown of antibiotics, target site modification, efflux pump overexpression, and the formation of biofilm are some of the mechanisms responsible for acquiring antimicrobial resistance (AMR). These mechanisms enable bacteria to evade or neutralize the effects of antimicrobial agents, complicating treatment options and increasing mortality rates. The rapid dissemination of resistance genes via horizontal gene transfer further exacerbates the problem, necessitating urgent intervention. Advanced AMR diagnostics are transforming the fight against antimicrobial resistance. Biosensors enable rapid, point-of-care detection; Cluster regularly interspaced short palindromic repeat (CRISPR) technologies offer precise identification of resistance genes; and mass spectrometry provides fast, accurate profiling. Automated systems streamline workflows and boost throughput, while flow cytometry delivers real-time, single-cell analysis of phenotypic resistance. Together, these innovations accelerate detection and support targeted antimicrobial stewardship, essential for combating the global AMR threat. This review covers the mechanisms underlying antimicrobial resistance (AMR) and recent advancements in AMR diagnostic technologies.202540544537
9813120.9931Antibacterial Discovery: 21st Century Challenges. It has been nearly 50 years since the golden age of antibiotic discovery (1945-1975) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to replace those rendered obsolete by drug resistance. Despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. Obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. This review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering 21st century medicines to combat multidrug resistant pathogens.202032353943
9560130.9930The History of Colistin Resistance Mechanisms in Bacteria: Progress and Challenges. Since 2015, the discovery of colistin resistance genes has been limited to the characterization of new mobile colistin resistance (mcr) gene variants. However, given the complexity of the mechanisms involved, there are many colistin-resistant bacterial strains whose mechanism remains unknown and whose exploitation requires complementary technologies. In this review, through the history of colistin, we underline the methods used over the last decades, both old and recent, to facilitate the discovery of the main colistin resistance mechanisms and how new technological approaches may help to improve the rapid and efficient exploration of new target genes. To accomplish this, a systematic search was carried out via PubMed and Google Scholar on published data concerning polymyxin resistance from 1950 to 2020 using terms most related to colistin. This review first explores the history of the discovery of the mechanisms of action and resistance to colistin, based on the technologies deployed. Then we focus on the most advanced technologies used, such as MALDI-TOF-MS, high throughput sequencing or the genetic toolbox. Finally, we outline promising new approaches, such as omics tools and CRISPR-Cas9, as well as the challenges they face. Much has been achieved since the discovery of polymyxins, through several innovative technologies. Nevertheless, colistin resistance mechanisms remains very complex.202133672663
8172140.9930From 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
9447150.9930Modern vaccine development via reverse vaccinology to combat antimicrobial resistance. With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review.202235642852
8173160.9930Advancing 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
9559170.9930CRISPR-Cas Systems in the Fight Against Antimicrobial Resistance: Current Status, Potentials, and Future Directions. BACKGROUND: Antimicrobial resistance (AMR) is a critical global health concern that threatens the efficacy of existing antibiotics and poses significant challenges to public health and the economy worldwide. This review explores the potential of CRISPR-Cas systems as a novel approach to combating AMR and examines current applications, limitations, and prospects. METHODS: A comprehensive literature search was conducted across multiple databases, including PubMed, Google Scholar, Scopus, and Web of Science, covering publications published from 2014 to August 2024. This review focuses on CRISPR-Cas technologies and their applications in AMR. RESULTS: CRISPR-Cas systems have demonstrated efficacy in combating antimicrobial resistance by targeting and eliminating antibiotic-resistance genes. For example, studies have shown that CRISPR-Cas9 can effectively target and eliminate colistin resistance genes in MCR-1 plasmids, restoring susceptibility to carbapenems in bacteria such as E. coli and Klebsiella pneumoniae. Further molecular findings highlight the impact of CRISPR-Cas systems on various bacterial species, such as Enterococcus faecalis, in which CRISPR systems play a crucial role in preventing the acquisition of resistance genes. The effectiveness of CRISPR-Cas in targeting these genes varies due to differences in CRISPR locus formation among bacterial species. For instance, variations in CRISPR loci influence the targeting of resistance genes in E. faecalis, and CRISPR-Cas9 successfully reduces resistance by targeting genes such as tetM and ermB. CONCLUSION: CRISPR-Cas systems are promising for fighting AMR by targeting and eliminating antibiotic-resistant genes, as demonstrated by the effective targeting of colistin resistance genes on MCR-1 plasmids and their similar activities. However, the effectiveness of CRISPR-Cas is affected by variations in the CRISPR loci among bacterial species. Challenges persist, such as optimizing delivery methods and addressing off-target effects to ensure the safety and precision of CRISPR-Cas systems in clinical settings.202439619730
8170180.9930Exploring 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
6691190.9930The antimicrobial resistance monitoring and research (ARMoR) program: the US Department of Defense response to escalating antimicrobial resistance. Responding to escalating antimicrobial resistance (AMR), the US Department of Defense implemented an enterprise-wide collaboration, the Antimicrobial Resistance Monitoring and Research Program, to aid in infection prevention and control. It consists of a network of epidemiologists, bioinformaticists, microbiology researchers, policy makers, hospital-based infection preventionists, and healthcare providers who collaborate to collect relevant AMR data, conduct centralized molecular characterization, and use AMR characterization feedback to implement appropriate infection prevention and control measures and influence policy. A particularly concerning type of AMR, carbapenem-resistant Enterobacteriaceae, significantly declined after the program was launched. Similarly, there have been no further reports or outbreaks of another concerning type of AMR, colistin resistance in Acinetobacter, in the Department of Defense since the program was initiated. However, bacteria containing AMR-encoding genes are increasing. To update program stakeholders and other healthcare systems facing such challenges, we describe the processes and impact of the program.201424795331