The Eukaryotic-Like Ser/Thr Kinase PrkC Regulates the Essential WalRK Two-Component System in
A central question in bacterial physiology is how bacteria sense and respond to their environment. The archetype of bacterial signaling systems is the two-component signaling system composed of a sensor protein histidine kinase that activates a transcription factor response regulator in response to a specific signal. In addition, bacteria also have signaling systems composed of eukaryotic-like Ser/Thr kinases and phosphatases. Even though these systems do not have dedicated transcription factors, they are capable of affecting gene expression. Here we show that a eukaryotic-like Ser/Thr kinase conserved in all sequenced Gram-positive bacteria converges with an essential two-component signaling system to regulate gene expression in the model organism Bacillus subtilis. We show that this eukaryotic-like Ser/Thr kinase phosphorylates the response regulator of a highly conserved and essential two-component signaling system, thereby increasing its activity. This phosphorylation results in the regulation of genes involved in the essential process of cell wall metabolism. Given that bacterial cell wall metabolism is the target of many known antibiotics, and mutations in both of these signaling systems change the antibiotic sensitivity of a number of important Gram-positive pathogens, we expect that our analysis will suggest novel insight into the emergence of antibiotic resistance.
Vyšlo v časopise:
The Eukaryotic-Like Ser/Thr Kinase PrkC Regulates the Essential WalRK Two-Component System in. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005275
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005275
Souhrn
A central question in bacterial physiology is how bacteria sense and respond to their environment. The archetype of bacterial signaling systems is the two-component signaling system composed of a sensor protein histidine kinase that activates a transcription factor response regulator in response to a specific signal. In addition, bacteria also have signaling systems composed of eukaryotic-like Ser/Thr kinases and phosphatases. Even though these systems do not have dedicated transcription factors, they are capable of affecting gene expression. Here we show that a eukaryotic-like Ser/Thr kinase conserved in all sequenced Gram-positive bacteria converges with an essential two-component signaling system to regulate gene expression in the model organism Bacillus subtilis. We show that this eukaryotic-like Ser/Thr kinase phosphorylates the response regulator of a highly conserved and essential two-component signaling system, thereby increasing its activity. This phosphorylation results in the regulation of genes involved in the essential process of cell wall metabolism. Given that bacterial cell wall metabolism is the target of many known antibiotics, and mutations in both of these signaling systems change the antibiotic sensitivity of a number of important Gram-positive pathogens, we expect that our analysis will suggest novel insight into the emergence of antibiotic resistance.
Zdroje
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