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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http://dx.doi.org/10.1016/j.chom.2024.09.004 | DOI Listing |
Biosens Bioelectron
January 2025
Department of Integrative Biotechnology, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea; Center for Biologics, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea. Electronic address:
The importance of in vitro diagnostics (IVDs) has significantly increased, driving the demand for rapid and sensitive diagnostic platforms. Molecular probes play a pivotal role in improving the sensitivity and accuracy of IVDs because of their target-specific signal transduction capabilities. Antibodies, which are commonly used as detection probes, face several challenges, including limited stability, high production costs, and low signal output.
View Article and Find Full Text PDFJ Bacteriol
January 2025
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
Unlabelled: Type IV pili (T4P) are important virulence factors that allow bacteria to adhere to and rapidly colonize their hosts. T4P are primarily composed of major pilins that undergo cycles of extension and retraction and minor pilins that initiate pilus assembly. Bacteriophages use T4P as receptors and exploit pilus dynamics to infect their hosts.
View Article and Find Full Text PDFPoult Sci
January 2025
Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan. Electronic address:
Escherichia coli (E. coli) is a widely distributed pathogenic bacterium that poses a substantial hazard to poultry, leading to the development of a severe systemic disease known as colibacillosis. Colibacillosis is involved in multimillion-dollar losses to the poultry industry each year worldwide.
View Article and Find Full Text PDFJ Theor Biol
January 2025
Institut de Biologie, Ecole Normale Superieure, Paris, 75005, France; School of Biological Sciences, Georgia Institute of Technology, Atlanta, 30332, GA, USA; Department of Biology, University of Maryland, College Park, 20742, MD, USA. Electronic address:
Virus population dynamics are driven by counter-balancing forces of production and loss. Whereas viral production arises from complex interactions with susceptible hosts, the loss of infectious virus particles is often approximated as a first-order kinetic process. As such, experimental protocols to measure infectious virus loss are not typically designed to identify non-exponential decay processes.
View Article and Find Full Text PDFFood Res Int
January 2025
Centro de Investigación en Alimentación y Desarrollo, A. C. Departamento de Microbiología y Biología Molecular. Av, Río Conchos S/N Parque Industrial. Z.C. 31570. Cd. Cuauhtémoc, Chihuahua, México. Electronic address:
Antimicrobial active packaging plays a key role in food quality and safety. The addition of antimicrobial agents in packaging production aims to release these agents from film to food, thereby preventing, reducing, or eliminating the contamination caused by pathogens or food spoilage microorganisms. This review provides an overview of the antimicrobial active packaging and gives an insight of the antimicrobials that have been used to manufacture antimicrobial active films.
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