Large-Scale Production of Cronobacter sakazakii Bacteriophage Φ CS01 in Bioreactors via a Two-Stage Self-Cycling Process

Lee Jin-Sun; Kim Gyeong-Hwuii; Kim Jaegon; Lim Tae-Hyun; Yoon Yongwon; 윤성식

doi:10.4014/jmb.2107.07017

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저자정보: Lee Jin-Sun (Department of Biological Science and Technology Yonsei University Wonju 26493 Korea) Kim Gyeong-Hwuii (Department of Biological Science and Technology Yonsei University Wonju 26493 Korea) Kim Jaegon (Department of Biological Science and Technology Yonsei University Wonju 26493 Korea) Lim Tae-Hyun (Department of Biological Science and Technology Yonsei University Wonju 26493 Korea) Yoon Yongwon (Department of Biological Science and Technology Yonsei University Wonju 26493 Korea) 윤성식 (연세대학교)

저널정보: 한국미생물생명공학회 Journal of Microbiology and Biotechnology Journal of Microbiology and Biotechnology 제31권 제10호

발행연도: 2021.10

수록면: 1,430 - 1,437 (8page)

DOI: 10.4014/jmb.2107.07017

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Cronobacter sakazakii is an opportunistic pathogenic bacterium found in powdered infant formula and is fatal to neonates. Antibiotic resistance has emerged owing to overuse of antibiotics. Therefore, demand for high-yield bacteriophages as an alternative to antibiotics has increased. Accordingly, we developed a modified mass-production method for bacteriophages by introducing a two-stage self-cycling (TSSC) process, which yielded high-concentration bacteriophage solutions by replenishing the nutritional medium at the beginning of each process, without additional challenge. pH of the culture medium was monitored in real-time during C. sakazakii growth and bacteriophage CS01 propagation, and the changes in various parameters were assessed. The pH of the culture medium dropped to 5.8 when the host bacteria reached the early log phase (OD540 = 0.3). After challenge, it decreased to 4.65 and then recovered to 4.94; therefore, we set the optimum pH to challenge the phage at 5.8 and that to harvest the phage at 4.94. We then compared phage production during the TSSC process in jar-type bioreactors and the batch culture process in shaker flasks. In the same volume of LB medium, the concentration of the phage titer solution obtained with the TSSC process was 24 times higher than that obtained with the batch culture process. Moreover, we stably obtained high concentrations of bacteriophage solutions for three cycles with the TSSC process. Overall, this modified TSSC process could simplify large-scale production of bacteriophage CS01 and reduce the unit cost of phage titer solution. These results could contribute to curing infants infected with antibiotic-resistant C. sakazakii.

#Bacteriophages #high cell density cultivation #Cronobacter sakazakii #two-stage self-cycling process #jar-type bioreactor #food safety

참고문헌 (21)

참고문헌 신청

Drudy D / 2006 / Enterobacter sakazakii : an emerging pathogen in powdered infant formula / Clin. Infect. Dis 42:996~1002

Hunter CJ / 2013 / Cronobacter : an emerging opportunistic pathogen associated with neonatal meningitis, sepsis and necrotizing enterocolitis / J. Perinatol 33:581~585

Hariri S / 2013 / Cronobacter sakazakii ST4 strains and neonatal meningitis, United States / Emerg. Infect. Dis 19:175~177

Wittebole X / 2014 / A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens / Virulence 5:226~235

Moghadam MT / 2020 / How phages overcome the challenges of drug resistant bacteria in clinical infections / Infect. Drug Resist 13:45~61

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