Fiche du document
3 novembre 2020
- doi: 10.1073/pnas.1920015117
- issn: 0027-8424
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1920015117
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/33087560
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1091-6490
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_3E34132DBF987
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
Sujets proches
Micrococcus pneumoniae Diplococcus pneumoniae Pneumococcus Genes--Expression Expressive behaviorCiter ce document
R.A. Sorg et al., « Synthetic gene-regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae. », Serveur académique Lausannois, ID : 10.1073/pnas.1920015117
Métriques
Partage / Export
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.