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Characterization of 29 newly isolated bacteriophages as a potential therapeutic agent against IMP-6-producing Klebsiella pneumoniae from clinical specimens.
Kondo, Kohei; Nakano, Satoshi; Hisatsune, Junzo; Sugawara, Yo; Kataoka, Michiyo; Kayama, Shizuo; Sugai, Motoyuki; Kawano, Mitsuoki.
Afiliación
  • Kondo K; Antimicrobial Resistance Research Center, National Institute of Infectious Diseases , Higashimurayama, Tokyo, Japan.
  • Nakano S; Antimicrobial Resistance Research Center, National Institute of Infectious Diseases , Higashimurayama, Tokyo, Japan.
  • Hisatsune J; Antimicrobial Resistance Research Center, National Institute of Infectious Diseases , Higashimurayama, Tokyo, Japan.
  • Sugawara Y; Antimicrobial Resistance Research Center, National Institute of Infectious Diseases , Higashimurayama, Tokyo, Japan.
  • Kataoka M; Department of Pathology, National Institute of Infectious Diseases , Toyama, Shinjuku-ku, Tokyo, Japan.
  • Kayama S; Antimicrobial Resistance Research Center, National Institute of Infectious Diseases , Higashimurayama, Tokyo, Japan.
  • Sugai M; Antimicrobial Resistance Research Center, National Institute of Infectious Diseases , Higashimurayama, Tokyo, Japan.
  • Kawano M; Department of Nutritional Sciences, Nakamura Gakuen University , Jonan-Ku, Fukuoka, Japan.
Microbiol Spectr ; : e0476122, 2023 Sep 19.
Article en En | MEDLINE | ID: mdl-37724861
Carbapenemase-producing Enterobacteriaceae (CPE) are one of the most detrimental species of antibiotic-resistant bacteria globally. Phage therapy has emerged as an effective strategy for the treatment of CPE infections. In western Japan, the rise of Klebsiella pneumoniae strains harboring the pKPI-6 plasmid encoding bla IMP-6 is of increasing concern. To address this challenge, we isolated 29 phages from Japanese sewage, specifically targeting 31 K. pneumoniae strains and one Escherichia coli strain harboring the pKPI-6 plasmid. Electron microscopy analysis revealed that among the 29 isolated phages, 21 (72.4%), 5 (17.2%), and 3 (10.3%) phages belonged to myovirus, siphovirus, and podovirus morphotypes, respectively. Host range analysis showed that 18 Slopekvirus strains within the isolated phages infected 25-26 K. pneumoniae strains, indicating that most of the isolated phages have a broad host range. Notably, K. pneumoniae strain Kp21 was exclusively susceptible to phage øKp_21, whereas Kp22 exhibited susceptibility to over 20 phages. Upon administering a phage cocktail composed of 10 phages, we observed delayed emergence of phage-resistant bacteria in Kp21 but not in Kp22. Intriguingly, phage-resistant Kp21 exhibited heightened sensitivity to other bacteriophages, indicating a "trade-off" for resistance to phage øKp_21. Our proposed phage set has an adequate number of phages to combat the K. pneumoniae strain prevalent in Japan, underscoring the potential of a well-designed phage cocktail in mitigating the occurrence of phage-resistant bacteria. IMPORTANCE The emergence of Klebsiella pneumoniae harboring the bla IMP-6 plasmid poses an escalating threat in Japan. In this study, we found 29 newly isolated bacteriophages that infect K. pneumoniae strains carrying the pKPI-6 plasmid from clinical settings in western Japan. Our phages exhibited a broad host range. We applied a phage cocktail treatment composed of 10 phages against two host strains, Kp21 and Kp22, which displayed varying phage susceptibility patterns. Although the phage cocktail delayed the emergence of phage-resistant Kp21, it was unable to hinder the emergence of phage-resistant Kp22. Moreover, the phage-resistant Kp21 became sensitive to other phages that were originally non-infective to the wild-type Kp21 strains. Our study highlights the potential of a well-tailored phage cocktail in reducing the occurrence of phage-resistant bacteria.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Microbiol Spectr Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Microbiol Spectr Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos