生物
肺炎克雷伯菌
微生物学
毒力
噬菌体
碳青霉烯
病毒学
大肠杆菌
抗生素
基因
遗传学
作者
Ella Rotman,Sandra McClure,Joshua Glazier,Jay Fuerte-Stone,Jonathan Foldi,Ali Erani,Rory McGann,Jack Arnold,Huaiying Lin,Sandra Valaitis,Mark Mimee
标识
DOI:10.1016/j.chom.2024.09.004
摘要
Antibiotic use can lead to the expansion of multi-drug-resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank for the tailored design of bacteriophage cocktails to treat multi-drug-resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identify host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank, we formulate phage combinations that eliminate K. pneumoniae with minimal phage resistance. Optimized cocktails selectively suppress the burden of K. pneumoniae in the mouse gut and drive the loss of key virulence factors that act as phage receptors. Phage-mediated diversification of bacterial populations in the gut leads to co-evolution of phage variants with higher virulence and broader host range. Altogether, the Klebsiella PhageBank charts a roadmap for phage therapy against a critical multidrug-resistant human pathogen.
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