Titre
Synthetic gene-regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
Sorg, R.A.
Auteure/Auteur
Gallay, C.
Auteure/Auteur
Van Maele, L.
Auteure/Auteur
Sirard, J.C.
Auteure/Auteur
Veening, J.W.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1091-6490
Statut éditorial
Publié
Date de publication
2020-11-03
Volume
117
Numéro
44
Première page
27608
Dernière page/numéro d’article
27619
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Streptococcus pneumoniae can cause disease in various human tissues and organs, including the ear, the brain, the blood, and the lung, and thus in highly diverse and dynamic environments. It is challenging to study how pneumococci control virulence factor expression, because cues of natural environments and the presence of an immune system are difficult to simulate in vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control in S. pneumoniae A selection platform is described that allows for straightforward identification of transcriptional regulatory elements out of combinatorial libraries. We present TetR- and LacI-regulated promoters that show expression ranges of four orders of magnitude. Based on these promoters, regulatory networks of higher complexity are assembled, such as logic AND gates and IMPLY gates. We demonstrate single-copy genome-integrated toggle switches that give rise to bimodal population distributions. The tools described here can be used to mimic complex expression patterns, such as the ones found for pneumococcal virulence factors. Indeed, we were able to rewire gene expression of the capsule operon, the main pneumococcal virulence factor, to be externally inducible (YES gate) or to act as an IMPLY gate (only expressed in absence of inducer). Importantly, we demonstrate that these synthetic gene-regulatory networks are functional in an influenza A virus superinfection murine model of pneumonia, paving the way for in vivo investigations of the importance of gene expression control on the pathogenicity of S. pneumoniae.
PID Serval
serval:BIB_3E34132DBF98
PMID
Open Access
Oui
Date de création
2020-10-30T10:18:07.128Z
Date de création dans IRIS
2025-05-20T15:56:50Z
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Nom
33087560_BIB_3E34132DBF98.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
2.38 MB
Format
Adobe PDF
PID Serval
serval:BIB_3E34132DBF98.P001
URN
urn:nbn:ch:serval-BIB_3E34132DBF987
Somme de contrôle
(MD5):93e5ee1257e184786f385d2680f96559