Phage and CRISPR based precision antimicrobials: a dual strategy against multidrug-resistant bacteria

Artificial intelligence and CRISPR-based approaches for targeted delivery of bacteriophages.

The rapid emergence of multidrug-resistant (MDR) bacteria has increased interest in bacteriophage therapy as a promising alternative to conventional antibiotics. Bacteriophages are host-specific bacterial viruses that selectively infect and destroy pathogenic bacterial strains. Recent developments in artificial intelligence (AI) and CRISPR-based technologies offer innovative approaches to address challenges such as narrow host range, rapid immune clearance, phage instability, bacterial resistance, and biofilm penetration barriers. By integrating AI-driven structural modeling with CRISPR-mediated genome editing, these methods enable the targeted delivery of bacteriophages. This review focuses on next-generation approaches that combine AI-assisted phage identification, host prediction, and therapeutic optimization with CRISPR-based genome engineering for targeted phage delivery and improved safety. Overall, this review highlights the potential of AI- and CRISPR-assisted phage therapy for the treatment of MDR bacterial infections. This review provides a systematic overview of bacteriophage biology, life cycle, and mechanisms of action, highlighting the influence of phage morphology on therapeutic performance, recent advances, current clinical and preclinical studies, and future perspectives. Although phage therapy shows considerable potential against MDR bacterial infections, several challenges related to delivery, safety, and clinical translation remain. The integration of AI and CRISPR technologies may improve phage selection, targeting specificity, and therapeutic performance. Continued research, clinical validation, and regulatory development will be essential for translating these advances into practical antimicrobial therapies.

CRISPR/Cas system as a novel therapeutic strategy to combat multi-drug-resistant bacteria

Phage Therapy Enhanced by Using Engineered Bacteriophages: A Powerful Antibacterial Tool to Address the Dilemma Posed by Multidrug-Resistant Bacterial Infections

The continuous slowdown in the research and development of new antibiotics and antibiotic overuse have turned the problem of antibacterial resistance into a global public health crisis. As a very promising alternative to multi-drug-resistant bacterial infection, phage therapy is receiving renewed attention. However, the inherent biological limitations of natural phages restrict their extensive clinical application. This review examines how synthetic biology can be harnessed to transform phages and to build the next generation of antibacterial therapies. We outline the main advantages of natural phages, including high host specificity, self-amplification, bactericidal activity and the ability to degrade biofilms. We also point out the bottlenecks of clinical applications of bacteriophages, such as narrow host range, rapid removal in the body and potential genetic safety risks. Moreover, we elaborate on the core synthetic biological tools used to overcome the above limitations, including CRISPR-Cas gene editing, receptor-binding protein reprogramming, functional load delivery and immunogenic regulation, and summarize the recent clinical progress and personalized treatment process. The increasing clinical evidence shows that synthetic biology can effectively overcome the inherent defects of natural bacteriophages, confirming the safety and initial efficacy of bacteriophage therapy. Engineered phages provide a practical strategy to meet the antimicrobial resistance challenge. Clinical applications of such phages will mainly depend on progress in production standardization, regulatory framework construction and scientific and reasonable joint treatment program development.

CRISPR-ENABLED ANTIMICROBIAL STRATEGIES: REDEFINING PRECISION THERAPY AGAINST MULTIDRUG RESISTANT PATHOGENS

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.

Bacteriophage Therapy as a Promising Substitute for Antibiotics: Current Advances, Clinical Applications, and Future Perspectives

The rapid emergence and global dissemination of antimicrobial-resistant (AMR) bacteria have significantly reduced the effectiveness of conventional antibiotics, posing a major threat to modern healthcare. The increasing prevalence of multidrug-resistant pathogens, coupled with the slow development of new antimicrobial agents, has renewed interest in alternative therapeutic strategies. Among these, bacteriophage (phage) therapy has re-emerged as a promising biological approach due to its ability to selectively infect and eliminate bacterial pathogens while preserving the normal microbiota. Unlike broad- spectrum antibiotics, bacteriophages exhibit high host specificity, self-replicate at the site of infection, and can effectively disrupt bacterial biofilms, making them particularly attractive for treating chronic and drug-resistant infections. This review critically examines the biological characteristics of bacteriophages, their mechanisms of antibacterial action, therapeutic applications, advantages, and current limitations. Recent advances in phage engineering, genome editing, phage cocktails, encapsulation technologies, and combination therapies with antibiotics are also discussed, highlighting their potential to improve treatment efficacy and overcome bacterial resistance. Furthermore, the review evaluates findings from recent preclinical and clinical studies, regulatory challenges, manufacturing considerations, and safety issues that currently limit the widespread clinical implementation of phage therapy. Although several scientific and regulatory hurdles remain, accumulating experimental and clinical evidence indicates that bacteriophage therapy could become an important component of future antimicrobial strategies. Continued multidisciplinary research, standardized clinical protocols, and well-designed randomized clinical trials are essential to establish its long-term efficacy and safety. With ongoing advances in molecular biology, synthetic biology, and precision medicine, bacteriophage therapy has the potential to complement or, in selected clinical situations, replace conventional antibiotics in the management of multidrug-resistant bacterial infections.

Plasmid-mediated multidrug resistance and the antibacterial potential of plant seed proteins

Chickpea proteins, especially the basic subunit (BS) fraction, demonstrated significant antibacterial activity against MDR pathogens, offering a promising natural alternative to conventional antibiotics.