2024-01-31 ノースウェスタン大学
この実験的な研究は、「ファージ療法」への関心の高まりを反映しており、抗生物質に耐性のある細菌を殺す新しい治療法としてデザイナーウイルスを開発するための重要な一歩です。研究は『Microbiology Spectrum』誌に掲載されました。
<関連情報>
- https://news.northwestern.edu/stories/2024/01/engineering-viruses-to-kill-deadly-pathogens/
- https://journals.asm.org/doi/10.1128/spectrum.02897-23
緑膿菌尾部ファージを合成生物学的手法で組み立て、臨床応用を目指す A synthetic biology approach to assemble and reboot clinically relevant Pseudomonas aeruginosa tailed phages
Thomas Ipoutcha, Ratanachat Racharaks, Stefanie Huttelmaier , Cole J. Wilson, Egon A. Ozer, Erica M. Hartmann
Microbiology Spectrum Published:31 January 2024
DOI:https://doi.org/10.1128/spectrum.02897-23
ABSTRACT
The rise in the frequency of antibiotic resistance has made bacterial infections, specifically Pseudomonas aeruginosa, a cause for greater concern. Phage therapy is a promising solution that uses naturally isolated phages to treat bacterial infections. Ecological limitations, which stipulate a discrete host range and the inevitable evolution of resistance, may be overcome through a better understanding of phage biology and the utilization of engineered phages. In this study, we developed a synthetic biology approach to construct tailed phages that naturally target clinically relevant strains of Pseudomonas aeruginosa. As proof of concept, we successfully cloned and assembled the JG024 and DMS3 phage genomes in yeast using transformation-associated recombination cloning and rebooted these two phage genomes in two different strains of P. aeruginosa. We identified factors that affected phage reboot efficiency like the phage species or the presence of antiviral defense systems in the bacterial strain. We have successfully extended this method to two other phage species and observed that the method enables the reboot of phages that are naturally unable to infect the strain used for reboot. This research represents a critical step toward the construction of clinically relevant, engineered P. aeruginosa phages.
