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

Autor:	Rotman E; Department of Microbiology, University of Chicago, Chicago, IL 60637, USA; Duchoissois Family Institute, University of Chicago, Chicago, IL 60637, USA., McClure S; 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., Glazier J; Department of Microbiology, University of Chicago, Chicago, IL 60637, USA; Duchoissois Family Institute, University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA., Fuerte-Stone J; Department of Microbiology, University of Chicago, Chicago, IL 60637, USA; Duchoissois Family Institute, University of Chicago, Chicago, IL 60637, USA; Committee on Microbiology, University of Chicago, Chicago, IL 60637, USA., Foldi J; Department of Microbiology, University of Chicago, Chicago, IL 60637, USA., Erani A; Department of Microbiology, University of Chicago, Chicago, IL 60637, USA., McGann R; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA., Arnold J; Department of Microbiology, University of Chicago, Chicago, IL 60637, USA; Duchoissois Family Institute, University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA., Lin H; Duchoissois Family Institute, University of Chicago, Chicago, IL 60637, USA., Valaitis S; Department of Obstetrics and Gynecology, Section of Urogynecology, University of Chicago, Chicago, IL 60637, USA., Mimee M; 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: mmimee@uchicago.edu.
Jazyk:	angličtina
Zdroj:	Cell host & microbe [Cell Host Microbe] 2024 Sep 27. Date of Electronic Publication: 2024 Sep 27.
DOI:	10.1016/j.chom.2024.09.004
Abstrakt:	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. Competing Interests: Declaration of interests A patent (63/370,XXX) related to this research has been filed by The University of Chicago, with M.M. and E.R. as inventors. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu