The evolutionary trade‐offs in phage‐resistant Klebsiella pneumoniae entail cross‐phage sensitization and loss of multidrug resistance

Summary Bacteriophage therapy is currently being evaluated as a critical complement to traditional antibiotic treatment. However, the emergence of phage resistance is perceived as a major hurdle to the sustainable implementation of this antimicrobial strategy. By combining comprehensive genomics and...

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Veröffentlicht in:Environmental microbiology 2021-12, Vol.23 (12), p.7723-7740
Hauptverfasser: Majkowska‐Skrobek, Grazyna, Markwitz, Pawel, Sosnowska, Ewelina, Lood, Cédric, Lavigne, Rob, Drulis‐Kawa, Zuzanna
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container_end_page 7740
container_issue 12
container_start_page 7723
container_title Environmental microbiology
container_volume 23
creator Majkowska‐Skrobek, Grazyna
Markwitz, Pawel
Sosnowska, Ewelina
Lood, Cédric
Lavigne, Rob
Drulis‐Kawa, Zuzanna
description Summary Bacteriophage therapy is currently being evaluated as a critical complement to traditional antibiotic treatment. However, the emergence of phage resistance is perceived as a major hurdle to the sustainable implementation of this antimicrobial strategy. By combining comprehensive genomics and microbiological assessment, we show that the receptor‐modification resistance to capsule‐targeting phages involves either escape mutation(s) in the capsule biosynthesis cluster or qualitative changes in exopolysaccharides, converting clones to mucoid variants. These variants introduce cross‐resistance to phages specific to the same receptor yet sensitize to phages utilizing alternative ones. The loss/modification of capsule, the main Klebsiella pneumoniae virulence factor, did not dramatically impact population fitness, nor the ability to protect bacteria against the innate immune response. Nevertheless, the introduction of phage drives bacteria to expel multidrug resistance clusters, as observed by the large deletion in K. pneumoniae 77 plasmid containing blaCTX‐M, ant(3″), sul2, folA, mph(E)/mph(G) genes. The emerging bacterial resistance to viral infection steers evolution towards desired population attributes and highlights the synergistic potential for combined antibiotic‐phage therapy against K. pneumoniae.
doi_str_mv 10.1111/1462-2920.15476
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subjects Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antibiotics
Antiinfectives and antibacterials
Bacteria
Bacteriophages - genetics
Biosynthesis
Clones
Defence mechanisms
Drug Resistance, Multiple
Evolutionary genetics
Exopolysaccharides
Genes
Humans
Immune response
Immunity
Innate immunity
Klebsiella
Klebsiella Infections - microbiology
Klebsiella pneumoniae
Klebsiella pneumoniae - genetics
Multidrug resistance
Mutation
Phage Therapy
Phages
Plasmids
Receptors
Virulence
Virulence factors
title The evolutionary trade‐offs in phage‐resistant Klebsiella pneumoniae entail cross‐phage sensitization and loss of multidrug resistance
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