Rapid design of bacteriophage cocktails to suppress the burden and virulence of gut-resident carbapenem-resistant Klebsiella pneumoniae.

Cell Host Microbe

Department of Microbiology, University of Chicago, Chicago, IL 60637, USA; Duchoissois Family Institute, University of Chicago, Chicago, IL 60637, USA; Committee on Molecular Metabolism and Nutrition, University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA. Electronic address:

Published: November 2024

AI Article Synopsis

  • Antibiotics can make bacteria in our bodies really tough, causing dangerous infections.
  • Researchers created something called the Klebsiella PhageBank, which helps design special viruses that can target and kill these tough bacteria.
  • This new method not only reduces the harmful bacteria but also helps in creating better virus versions to keep fighting against them effectively.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563920PMC
http://dx.doi.org/10.1016/j.chom.2024.09.004DOI Listing

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