Phage Therapy for Acinetobacter baumannii Infections: A Review on Advances in Classification, Applications, and Translational Roadblocks

This systematic review summarizes the latest research advances in phage therapy for drug-resistant Acinetobacter baumannii infections, including progress in phage classification, application strategies, and translational challenges, providing theoretical support and future directions for precise phage therapy.

 

Literature Overview
The article 'Phage Therapy for Acinetobacter baumannii Infections: A Review on Advances in Classification, Applications, and Translational Roadblocks' published in the journal Antibiotics comprehensively reviews and summarizes recent research progress in phage therapy against Acinetobacter baumannii infections, focusing on phage taxonomy, optimization of therapeutic strategies, and challenges in translational applications. The article provides a detailed analysis of the global public health threat posed by CRAB (Carbapenem-resistant Acinetobacter baumannii) and discusses the potential and limitations of phage therapy as an alternative antimicrobial approach.

Background Knowledge
Acinetobacter baumannii is a significant hospital-acquired pathogen that frequently causes pneumonia, bloodstream infections, and wound infections, particularly in intensive care units (ICUs). Due to its multidrug resistance (MDR) and pandrug resistance (PDR), traditional antibiotic treatments have limited efficacy, and carbapenem-resistant strains (CRAB) have become a global health crisis. Phage therapy has emerged as a promising strategy for combating drug-resistant bacteria because of its high specificity, minimal side effects, and self-amplifying properties. However, the narrow host range of phages, lack of standardized clinical translation protocols, and genetic engineering stability issues still limit their widespread application. Based on modern genomics and systematic evolutionary analysis, this review redefines phage classification and explores recent advances in phage cocktail therapy, phage-antibiotic synergy (PAS), and genetic engineering modifications, aiming to provide a framework for precision medicine in phage therapy for Acinetobacter baumannii infections.

 

 

Research Methods and Experiments
The article employs a systematic review approach, collecting and analyzing recent preclinical and clinical research data on phage therapy for Acinetobacter baumannii infections. By integrating genomics, structural biology, and animal models, the study explores phage classification, host specificity, optimization of therapeutic strategies, and genetic engineering approaches. The research also evaluates the therapeutic efficacy of phages in models of pneumonia, burn wounds, diabetic ulcers, bacteremia, and urinary tract infections, and analyzes the technical advantages of novel delivery systems such as phage aerosols and thermosensitive hydrogels.

Key Conclusions and Perspectives

• A phage classification system based on genomics replaces traditional morphological taxonomy, revealing host specificity and evolutionary relationships, thus laying the foundation for precision therapy.
• Phage cocktail therapy can cover more than 70% of tested bacterial strains, significantly reducing the risk of resistance to single phages (<5%).
• Phage-antibiotic synergy (PAS) demonstrates enhanced antibacterial efficacy in vitro and in animal models, allowing antibiotic doses to be reduced to as low as 1/4 of the MIC.
• Phage delivery via aerosol achieves a 42% alveolar deposition rate, while thermosensitive hydrogels enable sustained local release over 72 hours.
• Genetic engineering approaches, such as tail fiber recombination and CRISPR/Cas-mediated lysis cycle optimization, enhance the broad-spectrum efficacy of phages, although further validation of genetic stability is required.
• Phage therapy effectively clears pathogens and improves pathological damage in animal models, with additional immunomodulatory functions observed.
• Major current challenges include the limited host range, lack of standardized clinical translation criteria, and lagging regulatory frameworks.

Research Significance and Prospects
Phage therapy offers innovative solutions for combating CRAB infections, particularly in the context of rising multidrug-resistant strains. Future research should integrate metagenomic mining and synthetic biology to construct personalized phage therapy systems, while promoting standardized clinical trials and regulatory policy development to achieve precision medicine translation of phage therapy.

 

 

Conclusion
This article systematically reviews recent advances in phage therapy for Acinetobacter baumannii infections, highlighting its potential as an alternative to antibiotics. Phage therapy demonstrates promising results in vitro and in animal models through genomic reclassification, optimization of cocktails and synergistic treatments, and the introduction of genetic engineering approaches. However, challenges such as limited host range, lack of clinical standards, and incomplete regulatory systems remain significant barriers. Future research should focus on metagenomic mining, development of synthetic biology tools, and optimization of clinical translation pathways to transition phage therapy from experimental studies to clinical applications, particularly for precision treatment of multidrug-resistant and pandrug-resistant infections.

 

Yilin Wang, Liuyan Li, Yuqi Liang, Ying Ye, and Maozhang He. Phage Therapy for Acinetobacter baumannii Infections: A Review on Advances in Classification, Applications, and Translational Roadblocks. Antibiotics.