Genomic surveillance as a scalable framework for precision phage therapy against antibiotic-resistant pathogens

Area of Science:

• Microbiology and Infectious Diseases
• Genomics and Bioinformatics
• Therapeutic Development

Background:

• Antibiotic resistance, particularly from nosocomial pathogens like carbapenem-resistant Acinetobacter baumannii, poses a critical global health threat.
• Bacteriophage therapy offers a promising alternative to antibiotics, but the narrow host specificity of phages necessitates tailored treatment strategies.
• Developing effective phage therapeutics requires understanding the population dynamics and geographical distribution of target pathogens.

Purpose of the Study:

• To guide the development of precision phage cocktails targeting carbapenem-resistant Acinetobacter baumannii.
• To leverage phylogeographic analysis and high-throughput phage typing for regionalized phage collection development.
• To establish a scalable framework for precision phage therapy through genomic surveillance.

Main Methods:

• Conducted large-scale phylogeographic analysis of carbapenem-resistant Acinetobacter baumannii strains.
• Utilized high-throughput phage typing to assess phage efficacy against dominant regional strain types.
• Evaluated the efficacy of developed phage cocktails in in vitro and animal infection models.

Main Results:

• Identified dominant, geographically stable strain types of carbapenem-resistant Acinetobacter baumannii across different world regions.
• Demonstrated that region-specific phage collections can preemptively target the majority of local infections, as shown in Eastern Europe.
• Confirmed the efficacy of precision phage cocktails against prevalent bacterial strains in experimental settings.

Conclusions:

• Phylogeographic analysis combined with phage typing enables the creation of effective, region-specific phage cocktails.
• Genomic surveillance can identify patient cohorts benefiting from shared phage treatments across geographical scales.
• This approach provides a scalable and precise framework for combating antibiotic-resistant bacterial infections with phage therapy.