Deep longitudinal multi-omics analysis of Bordetella pertussis cultivated in bioreactors highlights medium starvations and transitory metabolisms, associated to vaccine antigen biosynthesis variations and global virulence regulation.

Autor:	Anziani P; Sanofi, Marcy-l'Étoile, France.; BIOASTER, Lyon, France., Becker J; BIOASTER, Lyon, France., Mignon C; BIOASTER, Lyon, France., Arnaud-Barbe N; Sanofi, Marcy-l'Étoile, France., Courtois V; Sanofi, Marcy-l'Étoile, France., Izac M; Sanofi, Marcy-l'Étoile, France., Pizzato R; Sanofi, Marcy-l'Étoile, France., Abi-Ghanem J; BIOASTER, Lyon, France., Tran VD; BIOASTER, Lyon, France., Sarafian M; BIOASTER, Lyon, France., Bunescu A; BIOASTER, Lyon, France., Garnier D; Sanofi, Marcy-l'Étoile, France., Abachin E; Sanofi, Marcy-l'Étoile, France., Renauld-Mongénie G; Sanofi, Marcy-l'Étoile, France., Guyard C; BIOASTER, Lyon, France.
Jazyk:	angličtina
Zdroj:	Frontiers in microbiology [Front Microbiol] 2023 Feb 14; Vol. 14, pp. 1036386. Date of Electronic Publication: 2023 Feb 14 (Print Publication: 2023).
DOI:	10.3389/fmicb.2023.1036386
Abstrakt:	Bordetella pertussis is the bacterial causative agent of whooping cough, a serious respiratory illness. An extensive knowledge on its virulence regulation and metabolism is a key factor to ensure pertussis vaccine manufacturing process robustness. The aim of this study was to refine our comprehension of B . pertussis physiology during in vitro cultures in bioreactors. A longitudinal multi-omics analysis was carried out over 26 h small-scale cultures of B . pertussis . Cultures were performed in batch mode and under culture conditions intending to mimic industrial processes. Putative cysteine and proline starvations were, respectively, observed at the beginning of the exponential phase (from 4 to 8 h) and during the exponential phase (18 h 45 min). As revealed by multi-omics analyses, the proline starvation induced major molecular changes, including a transient metabolism with internal stock consumption. In the meantime, growth and specific total PT, PRN, and Fim2 antigen productions were negatively affected. Interestingly, the master virulence-regulating two-component system of B . pertussis (BvgASR) was not evidenced as the sole virulence regulator in this in vitro growth condition. Indeed, novel intermediate regulators were identified as putatively involved in the expression of some virulence-activated genes ( vags ). Such longitudinal multi-omics analysis applied to B . pertussis culture process emerges as a powerful tool for characterization and incremental optimization of vaccine antigen production. Competing Interests: PA, NA-B, VC, MI, RP, DG, EA, and GR-M were employed by Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Anziani, Becker, Mignon, Arnaud-Barbe, Courtois, Izac, Pizzato, Abi-Ghanem, Tran, Sarafian, Bunescu, Garnier, Abachin, Renauld-Mongénie and Guyard.)
Databáze:	MEDLINE
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