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INDM 3007

INDM 3007. Lecture 8. Bacteria use many types of regulation at the same time in order to make decisions. Adequate regulation of the repetoire of available genes is critical to survive in hostile environments to compete with other bacteria for the same resources.

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INDM 3007

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  1. INDM 3007 Lecture 8

  2. Bacteria use many types of regulation at the same time in order to make decisions Adequate regulation of the repetoire of available genes is critical to survive in hostile environments to compete with other bacteria for the same resources Example of this is the decision making pathway of Bacillus subtilis

  3. Normal growth of bacillus subtilis cell division sporulation ? Transition state Integration and evaluation of information Should I stay or Should I go? Nutrient availability Cell density Cell cycle Chemo-physical information

  4. The initial sequence of events involves a phosphorelay system Signal B Signal A KinB KinA Phosphate is transferred via SpoOF and SpoOB to the transcriptional regulator SpoOA The flow of phosphate is determined by two kinases which respond to environmental signals How does Bacillus subtilis make decisions?

  5. Allows phosphorylation state of Spo proteins to be adjusted by the use of phosphatases responding to environmental signals Why use a complicated signal transduction pathway? Phosphatases allow the pathway to shutdown when conditions are not right for sporulation The phosphorylation state of SpoOA is dependent on environmental signals

  6. abr spoOF SpoOA~P represses transcription of spoOA, spoOF and abr from promoters using the sigA dependent promoters spoOA SpoOA~P is both a repressor and a transcriptional activator SigA is the normal housekeeping sigma factor of Bacillus subtilis

  7. abr BUT Also less production of the repressor Abr This means that as SpoOA becomes phosphorylated, less SpoOF and SpoOA is being made This leads to a reduction in phosphate transfer to SpoOA: negative feedback What does Abr do?

  8. abr AbR represses the expression of SigH, an alternative sigma factor sigH Chain of events thusfar: Environmental signals increase phosphorylation of SpoOA, SpoOA~P represses expression of abr, which results in expression of sigH So what does SigH do?

  9. SpoOA and spoOF have TWO promoters, one transcribed with SigA, the other with SigH Expression of kinA the kinase phosphorylating SpoOF is transcribed from a sigH promoter kinA While SpoOA represses transcription from sigA promoters, it activates transcription from sigH promoters! spoOF spoOA So what does this mean?

  10. Signal B Signal A KinB KinA With few positive environmental signals SpoOA~P reduces levels of SpoOA and SpoOF, leading to a reduction of phosphate flow through pathway. Due to repression of SigA dependent spoOA and spoOF promoters No commitment to sporulate

  11. Signal B Signal A KinB KinA With many positive signals, high levels of SpoOA~P repress expression of abr, resulting in production of SigH SpoOA~P activates transcription from SigH promoters Rapid increase in SpoOA, SpoOF and KinA Increase in phosphate flow through pathway This leads to exponentially increased levels of SpoOA~P, resulting in activation of the first group of sporulation genes

  12. The phosphorylation state of SpoOA is controlled by Activity of KinA and KinB Phosphatases Controlled by environmental signals Intracellular concentration of SpoOF, SpoOA and KinA Controlled by SpoOA~P, ABR and SigH The result is a very sensitive pathway, which will only commit to sporulation when a multitude of environmental signals indicate that it is time to do so

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