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Article

Regulation of Clostridium tetani Neurotoxin Expression by Culture Conditions

1
Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, The Netherlands
2
Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy l’Etoile, France
3
Department of Chemical and Physical Health Risks, Sciensano, 14 Rue Juliette Wytsman, 1050 Brussels, Belgium
4
IVIDATA Life Sciences, 79-83 Rue Baudin, 92300 Levallois Perret, France
*
Author to whom correspondence should be addressed.
Toxins 2022, 14(1), 31; https://doi.org/10.3390/toxins14010031
Received: 29 November 2021 / Revised: 22 December 2021 / Accepted: 29 December 2021 / Published: 2 January 2022
(This article belongs to the Section Bacterial Toxins)
Background: Ensuring consistency of tetanus neurotoxin (TeNT) production by Clostridium tetani could help to ensure consistent product quality in tetanus vaccine manufacturing, ultimately contributing to reduced animal testing. The aim of this study was to identify RNA signatures related to consistent TeNT production using standard and non-standard culture conditions. Methods: We applied RNA sequencing (RNA-Seq) to study C. tetani gene expression in small-scale batches under several culture conditions. Results: We identified 1381 time-dependent differentially expressed genes (DEGs) reflecting, among others, changes in growth rate and metabolism. Comparing non-standard versus standard culture conditions identified 82 condition-dependent DEGs, most of which were specific for one condition. The tetanus neurotoxin gene (tetX) was highly expressed but showed expression changes over time and between culture conditions. The tetX gene showed significant down-regulation at higher pH levels (pH 7.8), which was confirmed by the quantification data obtained with the recently validated targeted LC-MS/MS approach. Conclusions: Non-standard culture conditions lead to different gene expression responses. The tetX gene appears to be the best transcriptional biomarker for monitoring TeNT production as part of batch-to-batch consistency testing during tetanus vaccine manufacturing. View Full-Text
Keywords: tetanus vaccine; next-generation sequencing; consistency approach; gene expression; targeted LC-MS/MS; 3Rs principles tetanus vaccine; next-generation sequencing; consistency approach; gene expression; targeted LC-MS/MS; 3Rs principles
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MDPI and ACS Style

Pennings, J.L.A.; Abachin, E.; Esson, R.; Hodemaekers, H.; Francotte, A.; Claude, J.-B.; Vanhee, C.; Uhlrich, S.; Vandebriel, R.J. Regulation of Clostridium tetani Neurotoxin Expression by Culture Conditions. Toxins 2022, 14, 31. https://doi.org/10.3390/toxins14010031

AMA Style

Pennings JLA, Abachin E, Esson R, Hodemaekers H, Francotte A, Claude J-B, Vanhee C, Uhlrich S, Vandebriel RJ. Regulation of Clostridium tetani Neurotoxin Expression by Culture Conditions. Toxins. 2022; 14(1):31. https://doi.org/10.3390/toxins14010031

Chicago/Turabian Style

Pennings, Jeroen L.A., Eric Abachin, Raphaël Esson, Hennie Hodemaekers, Antoine Francotte, Jean-Baptiste Claude, Céline Vanhee, Sylvie Uhlrich, and Rob J. Vandebriel. 2022. "Regulation of Clostridium tetani Neurotoxin Expression by Culture Conditions" Toxins 14, no. 1: 31. https://doi.org/10.3390/toxins14010031

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