Lytic bacteriophages active in urine against multidrug-resistant clinically derived Klebsiella pneumoniae causing

Ruxandra Calin1, Blanca Bernabeu Vilaplana2, Judeline Gedeon3

  • 1Mucosal Inflammation and Immunity Team, Université Paris Cité, CNRS, Inserm, Institut Cochin, F-75014 Paris, France & Department of Immunology, Institut Pasteur, Paris, France; AP-HP Sorbonne-Université, Hôpital Tenon, Service Maladies Infectieuses et Tropicales, Paris, France.

Abstract

Insights

Three novel bacteriophages were identified that effectively target multidrug-resistant Klebsiella pneumoniae causing urinary tract infections (UTIs). These phages demonstrated enhanced lytic activity in human urine, supporting their potential for therapeutic development against resistant infections.

Area of Science:

  • Microbiology
  • Virology
  • Infectious Diseases

Background:

  • Multidrug-resistant (MDR) Klebsiella pneumoniae is a growing threat, particularly in recurrent urinary tract infections (UTIs).
  • Bacteriophage therapy offers a potential alternative to antibiotics for treating MDR bacterial infections.

Purpose of the Study:

  • To isolate and characterize bacteriophages effective against a clinical MDR K. pneumoniae strain responsible for recurrent UTIs.
  • To evaluate the activity of these bacteriophages under conditions mimicking the human urinary tract.

Main Methods:

  • Isolation and characterization of three lytic bacteriophages targeting an ESBL-producing K. pneumoniae.
  • Genome sequencing, electron microscopy, stability assays, growth curves, and host-range analysis.
  • Quantification of phage activity in both LB medium and human urine.

Main Results:

  • Three distinct lytic phages (EDIRA083, EDIRA088, EDIRA092) were identified, lacking lysogeny, virulence, or antibiotic-resistance genes.
  • Capsule, LPS, and LamB were identified as receptors for two phages; one phage infected 29% of tested strains.
  • Phage lytic activity was significantly higher and more sustained in human urine compared to LB medium.

Conclusions:

  • Three genetically distinct lytic phages targeting MDR K. pneumoniae were successfully identified.
  • The demonstrated activity of these phages in urine supports their potential as therapeutic candidates for Klebsiella UTIs.
  • Further evaluation is warranted for the development of phage-based therapies against MDR K. pneumoniae infections.

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