Phages against Noncapsulated Klebsiella pneumoniae: Broader Host range, Slower Resistance
| Autor: | Lourenço, Marta, Osbelt, Lisa, Passet, Virginie, Gravey, François, Megrian, Daniela, Strowig, Till, Rodrigues, Carla, Brisse, Sylvain |
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| Přispěvatelé: | Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Helmholtz Centre for Infection Research (HZI), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was mainly supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) project CRISPR-ATTACK (Advancing CRISPR antimicrobials to combat the bacterial pathogen Klebsiella pneumoniae) under the French Agence Nationale de la Recherche grant ANR-18-JAM2-0004-04, S.B. and 01KI1824 to T.S. C.R. was also supported financially by a Pasteur-Roux fellowship by the Institut Pasteur. The BEBP laboratory is supported by the French Government Investissement d’Avenir Program Laboratoire d’Excellence, Integrative Biology of Emerging Infectious Diseases (ANR10LABX62IBEID). T.S. was also supported by the Federal Ministry of Science under the project DF-AMR2:DECOLONIZE (01KI2131), JPI-AMR Germany (01KI1824) as well as by the German Center for Infection Research (DZIF, TTU 06.826)., We thank Olaya Rendueles Garcia and Eduardo Rocha for sharing the mutant strains that were used for the anti-Kd phage isolation. We thank the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA, especially Marc Monot, Elodie Turc, Laure Lemée and Georges Haustant, for the sequencing project management, the preparation of the genomic libraries, and the sequencing. We thank Melanie Hennart for the bioinformatics methodological input and Anne-Marie Wehenkel for the help with the protein analyses. We are grateful to Jin-Town Wang for sharing the strain NTUH-K2044. We thank Quentin Lamy-Besnier, Chiara Crestani, and Olaya Rendueles Garcia for the critical reading of the manuscript., ANR-18-JAM2-0004,CRISPRattacK(2018), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010) |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Klebsiella pneumoniae
in vivo bacteriophages phage therapy bacteriophage-bacteria interactions phage resistance [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases genomics host range bacteriophage therapy antimicrobial resistance noncapsulated mutants phage-bacteria interactions |
| Zdroj: | Microbiology Spectrum Microbiology Spectrum, In press, ⟨10.1128/spectrum.04812-22⟩ |
| ISSN: | 2165-0497 |
| DOI: | 10.1128/spectrum.04812-22⟩ |
| Popis: | International audience; Klebsiella pneumoniae (Kp), a human gut colonizer and opportunistic pathogen, is a major contributor to the global burden of antimicrobial resistance. Virulent bacteriophages represent promising agents for decolonization and therapy. However, the majority of anti-Kp phages that have been isolated thus far are highly specific to unique capsular types (anti-K phages), which is a major limitation to phage therapy prospects due to the highly polymorphic capsule of Kp. Here, we report on an original anti-Kp phage isolation strategy, using capsule-deficient Kp mutants as hosts (anti-Kd phages). We show that anti-Kd phages have a broad host range, as the majority are able to infect noncapsulated mutants of multiple genetic sublineages and O-types. Additionally, anti-Kd phages induce a lower rate of resistance emergence in vitro and provide increased killing efficiency when in combination with anti-K phages. In vivo, anti-Kd phages are able to replicate in mouse guts colonized with a capsulated Kp strain, suggesting the presence of noncapsulated Kp subpopulations. The original strategy proposed here represents a promising avenue that circumvents the Kp capsule host restriction barrier, offering promise for therapeutic development.IMPORTANCE Klebsiella pneumoniae (Kp) is an ecologically generalist bacterium as well as an opportunistic pathogen that is responsible for hospital-acquired infections and a major contributor to the global burden of antimicrobial resistance. In the last decades, limited advances have been made in the use of virulent phages as alternatives or complements to antibiotics that are used to treat Kp infections. This work demonstrates the potential value of an anti-Klebsiella phage isolation strategy that addresses the issue of the narrow host range of anti-K phages. Anti-Kd phages may be active in infection sites in which capsule expression is intermittent or repressed or in combination with anti-K phages, which often induce the loss of capsule in escape mutants. |
| Databáze: | OpenAIRE |
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