QseC
| Sensor protein qseC ( Escherichia coli K12) | ||
|---|---|---|
| Mass / length primary structure | 449 amino acids | |
| Identifier | ||
| Gene name (s) | qseC | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 2.7.13.3 , protein kinase | |
| Response type | Phosphorylation of a histidine residue | |
| Substrate | ATP + protein L-histidine | |
| Products | ADP + protein-N-phospho-L-histidine | |
| Occurrence | ||
| Homology family | Sensor histidine kinase | |
| Parent taxon | bacteria | |
The sensor protein QseC is an enzyme found in the cell membrane of bacteria . Via the regulatory protein QseB , it activates the transcription of several, among other things, virulent genes. So it starts the expression of FLHC protein which for the activation of the flagella - biosynthesis is responsible. This reaction is a partial step in the transmission of the signal to the bacterium that there are worthwhile host cells on the outside, with the result that the bacterium increases the production of further proteins with a virulent effect, so to speak `` to attack ''.
QseC is essential for the virulence of enterohaemorrhagic Escherichia coli ( EHEC ) and regulates the expression of virulent genes in some other pathogenic strains such as Salmonella typhimurium . The enzyme is therefore a very promising target for the pharmaceutical industry with the aim of developing novel antibiotics .
Signal transmission
The sensor protein QseC is a histidine kinase that enables communication between a prokaryotic pathogen and a eukaryotic host , i.e. signal transduction between two different animal kingdoms (inter-kingdom signaling). The QseC located in the bacterial cell membrane binds the hormones adrenaline and noradrenaline released by the host as well as the bacterial hormone AI-3. As a result of this binding, QseC is first autophosphorylated and then the regulatory protein QseB is phosphorylated . This then directly activates the transcription of target genes. It is therefore a two-component system .
The target genes of QseC include genes responsible for cell adhesion , motility genes and iron uptake, as well as the Shiga toxin . This explains in part the key role QseC plays in the virulence of EHEC. Since QseC also binds the pathogen's own hormone AI-3, it is an example of a receptor that integrates signals from different animal kingdoms.
Antibiotics
QseC is a potentially promising target for the development of a new class of antibiotics. This is due to the fact that the inhibition of QseC does not suppress the growth of pathogens but does inhibit the virulence. This enables future antibiotics to develop their full potential without putting themselves under selective pressure. Because the main limitation of today's antibiotics is the development of antibiotic resistance caused by pathogens.
Some successes have already been achieved in this area. In 2008, a US research group in the University of Texas found an inhibitor molecule LED209 that inhibits the autophosphorylation of QseC and consequently prevents the expression of virulence genes. The effect of LED209 was demonstrated using mouse models. The molecule will serve as the starting point for the development of antibiotics against multiple bacterial pathogens.
Individual evidence
- ↑ UniProt P40719
- ↑ Clarke MB, Hughes DT, Zhu C, Boedeker EC, Sperandio V: The QseC sensor kinase: a bacterial adrenergic receptor . In: Proc. Natl. Acad. Sci. USA . 103, No. 27, July 2006, pp. 10420-5. doi : 10.1073 / pnas.0604343103 . PMID 16803956 . PMC 1482837 (free full text).
- ↑ Clarke MB, Sperandio V: Transcriptional regulation of flhDC by QseBC and sigma (FliA) in enterohaemorrhagic Escherichia coli . In: Mol. Microbiol. . 57, No. 6, September 2005, pp. 1734-49. doi : 10.1111 / j.1365-2958.2005.04792.x . PMID 16135237 . Erratum in: Mol Microbiol. 58 (4): 1203, 2005.
- ↑ Hughes DT, Sperandio V: Inter-kingdom signaling: communication between bacteria and Their hosts . In: Nat. Rev. Microbiol. . 6, No. 2, February 2008, pp. 111-20. doi : 10.1038 / nrmicro1836 . PMID 18197168 .
- ↑ Rasko DA, Moreira CG, Li de R, et al : Targeting QseC signaling and virulence for antibiotic development . In: Science (journal) . 321, No. 5892, August 2008, pp. 1078-80. doi : 10.1126 / science.1160354 . PMID 18719281 . PMC 2605406 (free full text).