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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Phage Biology
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1468686
This article is part of the Research Topic Phage-Based Strategies for Foodborne Pathogen Mitigation and Detection View all 5 articles

Targeted Dual-Receptor Phage Cocktail Against Cronobacter sakazakii: Insights into Phage-Host Interactions and Resistance Mechanisms

Provisionally accepted
Seongok Kim Seongok Kim 1,2Bokyung Son Bokyung Son 3Yeran Kim Yeran Kim 4Hakdong Shin Hakdong Shin 1,2*Sangryeol Ryu Sangryeol Ryu 4,5,6*
  • 1 Department of Food Science & Biotechnology, College of Life Science, Sejong University, Seoul, Republic of Korea
  • 2 Carbohydrate Bioproduct Research Center, Sejong University, Seoul, Republic of Korea
  • 3 Department of Food Biotechnology, Dong-A University, Busan, Republic of Korea
  • 4 Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
  • 5 Department of Food and Animal Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
  • 6 Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea

The final, formatted version of the article will be published soon.

    Cronobacter sakazakii is a notorious foodborne pathogen, frequently contaminating powdered infant formula and causing life-threatening diseases in infants. The escalating emergence of antibioticsresistant mutants has led to increased interest in using bacteriophage as an alternative antimicrobial agent. We isolated two virulent bacteriophages, CR8 and S13, which specifically target C. sakazakii. Morphological and genomic analyses revealed that both CR8 and S13 belong to the class Caudoviricetes of phages with contractile tails, but they differ at DNA levels. Phage CR8 and phage S13 utilize flagella and LPS, respectively, to adhere to host cells. Bacterial challenge assay demonstrated delayed emergence of the resistant mutant by prolonging period of growth inhibition as well as stronger lytic activity of a phage cocktail consisting of CR8 and S13 than the single phage treatment. Phenotypic analysis of the phage cocktail resistant strain, designated as CSR strain, revealed that the resistance resulted from the impaired receptor proteins for phage, such as defects in motility and alteration in LPS structure. Consistent with the idea that acquiring phage resistance entails a fitness tradeoff, CSR strain exhibited significant attenuation in invading human intestinal epithelial Caco-2 cells compared to WT cells. These findings suggest that the development of the phage cocktail targeting distinct host receptors can serve as a promising antimicrobial strategy to effectively control C. sakazakii.

    Keywords: Cronobacter sakazakii, phage cocktail, Flagella, Lipopolysaccharides, Bacteriophage therapy, phage resistance, Fitness tradeoff

    Received: 22 Jul 2024; Accepted: 22 Nov 2024.

    Copyright: © 2024 Kim, Son, Kim, Shin and Ryu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hakdong Shin, Department of Food Science & Biotechnology, College of Life Science, Sejong University, Seoul, Republic of Korea
    Sangryeol Ryu, Department of Food and Animal Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.