AI Networking Cookbook: Practical recipes for AI-assisted network automation and development
TL;DR
This study investigates the CRISPR-Cas framework’s potential as a cutting-edge tactic to fight antimicrobial resistance, and finds that the efficiency of CRISPR-Cas is diminished in some bacterial strains due to variations in their CRISPR loci.
Overall, CRISPR-based antimicrobial therapy represents a transformative approach to precision infectious disease management, with continued technological innovation, interdisciplinary collaboration, and robust clinical validation expected to facilitate its safe, effective, and clinically accessible implementation against multidrug-resistant pathogens.
This review critically examines bacteriophage-based antimicrobials, CRISPR-Cas therapeutic systems, and their emerging integration as CRISPR-armed phages, highlighting their comparative advantages, current limitations, and future potential as promising targeted antimicrobial approach platforms requiring further clinical validation.
Drug-resistant fungal pathogens pose a growing public health threat, causing millions of infections and deaths annually. Limited antifungal drug classes and rising resistance highlight the urgent need for novel therapies. CRISPR-Cas systems offer sequence-specific antimicrobial potential, but their efficacy is influenced by organism-specific DNA repair outcomes. Here, we demonstrate that in Candida albicans, which predominantly relies on homology-directed repair (HDR), both repair template availability and DNA repair enzyme activity critically determine Cas9-induced lethality. By providing Trojan Horse donor DNA repair templates when targeting essential and DNA repair genes, we show that Cas9 lethality can be selectively tuned. Furthermore, multiplexed gRNA targeting to modulate DNA repair capacity reveals strong synergistic interactions when co-targeting HDR components, which is corroborated by enhanced killing in HDR-compromised strains. These results establish DNA repair as a programmable determinant of CRISPR-Cas antifungal activity and provide a mechanistic framework for combinatorial targeting strategies, advancing the development of CRISPR-Cas antifungals. GRAPHICAL ABSTRACT
Antimicrobial resistance (AMR) has become one of the defining threats to survival in intensive and neonatal intensive care units, where vulnerable hosts, invasive devices, and heavy empirical antibiotic exposure converge to select for multidrug- and extensively drug-resistant ESKAPE and non-aeruginosa Pseudomonas pathogens. We conducted a narrative-scoping synthesis of the peer-reviewed literature identified through targeted searches and, restricted to English-language articles addressing AMR mechanisms and next-generation, non-traditional therapeutics in critical care; reference lists were hand-searched, and findings were organized thematically rather than statistically pooled. Four convergent, non-traditional pillars emerged — programmable CRISPR-Cas and CRISPRi genomic tools, monoclonal antibodies and bioconjugates, antimicrobial and anticancer peptides (notably proline-rich peptides), and stimuli-responsive nanozymes and exosomal carriers — each capable of bypassing classical resistance mechanisms while, at least in preclinical models, sparing commensal microbiota. Persistent translational barriers include bedside diagnostic blindness to biofilm-embedded organisms, an unresolved neonatal and pediatric pharmacokinetic/pharmacodynamic void, and stewardship frameworks that still largely ignore the human resistome. Bridging bench-to-bedside gaps will require standardized biofilm models, dedicated pediatric PK/PD trials, artificial-intelligence-assisted therapeutic design, and microbiome-conscious stewardship, particularly given resource disparities across low- and middle-income settings.
Highlights • CRISPR-Cas systems enable programmable, sequence-specific elimination of antimicrobial resistance genes.• Diverse Cas effectors (Cas9, Cas3, Cas12a, Cas13, Cas14) and delivery platforms (phages, plasmids, nanoparticles, OMVs) expand therapeutic versatility.• CRISPRi offers reversible resistance suppression, while AI-guided design and toxin-antitoxin systems enhance efficacy and safety.• In vivo models confirm significant reduction of resistant pathogens, supporting clinical translational potential.• Key challenges remain in off-target effects, manufacturing, and regulatory approval for human use.
Antimicrobial resistance (AMR) has emerged as one of the greatest global public health threats, compromising the effectiveness of antibiotics and jeopardizing advances in modern medicine. The extensive use and misuse of antimicrobial agents in human medicine, veterinary practice, agriculture, and aquaculture have accelerated the emergence and spread of multidrug-resistant microorganisms. Because resistant pathogens, antibiotic residues, and resistance genes continuously circulate among humans, animals, and the environment, AMR is now recognized as a complex One Health challenge requiring coordinated, multidisciplinary solutions. However, conventional strategies, including the development of new antibiotics and antimicrobial stewardship programs, are increasingly constrained by rapid microbial adaptation, biofilm formation, delayed diagnosis, and the declining antibiotic discovery pipeline. Nanotechnology has emerged as a promising interdisciplinary platform capable of addressing several limitations of conventional antimicrobial approaches. Nanomaterials possess intrinsic broad-spectrum antimicrobial activity, enhance targeted drug delivery, improve biofilm eradication, and enable rapid pathogen detection through advanced nanodiagnostic systems. Furthermore, integrating nanotechnology with artificial intelligence, machine learning, and smart biosensing technologies is accelerating the development of precision antimicrobial therapies and real-time AMR surveillance systems. This review discusses the AMR crisis from a One Health perspective and summarizes recent advances in antimicrobial nanomaterials, nanodrug delivery systems, antibiofilm strategies, and nanodiagnostics. Current translational challenges and future perspectives are also highlighted, emphasizing the potential of nanotechnology to support sustainable AMR management across interconnected human, animal, and environmental sectors.
We use cookies to run the site and, with your consent, for analytics and to show ads. See our Cookie Policy.