Synthetic gene regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae
| Autor: | Clement Gallay, Robin A. Sorg, Jan-Willem Veening |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
030306 microbiology Virulence Human pathogen Promoter Computational biology Biology medicine.disease_cause Virulence factor 03 medical and health sciences chemistry.chemical_compound Synthetic biology chemistry Gene expression Streptococcus pneumoniae medicine TetR 030304 developmental biology |
| DOI: | 10.1101/834689 |
| Popis: | Streptococcus pneumoniaecan 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 simulatein vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control inS. 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 and IMPLY gates. Finally, 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, paving the way forin vivoinvestigations of the importance of gene expression control on the pathogenicity ofS. pneumoniae. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|