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Synchronization of Caulobacter Crescentus for Investigation of the Bacterial Cell Cycle
Published on: April 8, 2015
Growth control switch by a DNA-damage-inducible toxin-antitoxin system in Caulobacter crescentus
Clare L Kirkpatrick1, Daniel Martins1, Peter Redder1
1Department of Microbiology &Molecular Medicine, Institute of Genetics &Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Rue Michel-Servet 1, 1211 Genève 4, Switzerland.
Abstract:
Bacterial toxin-antitoxin systems (TASs) are thought to respond to various stresses, often inducing growth-arrested (persistent) sub-populations of cells whose housekeeping functions are inhibited. Many such TASs induce this effect through the translation-dependent RNA cleavage (RNase) activity of their toxins, which are held in check by their cognate antitoxins in the absence of stress. However, it is not always clear whether specific mRNA targets of orthologous RNase toxins are responsible for their phenotypic effect, which has made it difficult to accurately place the multitude of TASs within cellular and adaptive regulatory networks. Here, we show that the TAS HigBA of Caulobacter crescentus can promote and inhibit bacterial growth dependent on the dosage of HigB, a toxin regulated by the DNA damage (SOS) repressor LexA in addition to its antitoxin HigA, and the target selectivity of HigB's mRNA cleavage activity. HigB reduced the expression of an efflux pump that is toxic to a polarity control mutant, cripples the growth of cells lacking LexA, and targets the cell cycle circuitry. Thus, TASs can have outcome switching activity in bacterial adaptive (stress) and systemic (cell cycle) networks.
Insights
Bacterial toxin-antitoxin systems (TASs) can switch between promoting and inhibiting bacterial growth. This outcome switching depends on toxin dosage and mRNA targets, influencing stress response and cell cycle networks.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Bacterial toxin-antitoxin systems (TASs) are crucial for stress response, often inducing growth arrest via toxin-mediated RNA cleavage.
- The precise mRNA targets and regulatory roles of many TASs remain unclear, hindering their integration into cellular networks.
Purpose of the Study:
- To investigate the regulatory role and target specificity of the HigBA toxin-antitoxin system in Caulobacter crescentus.
- To determine how HigB toxin dosage and mRNA targets influence bacterial growth and cellular processes.
Main Methods:
- Analysis of the HigBA toxin-antitoxin system in Caulobacter crescentus.
- Investigating the impact of HigB toxin dosage and LexA regulation on bacterial growth.
- Identifying mRNA targets of HigB's RNA cleavage activity.
Main Results:
- The HigBA system exhibits outcome-switching activity, promoting or inhibiting bacterial growth based on HigB dosage.
- HigB is regulated by the DNA damage (SOS) repressor LexA, in addition to its antitoxin HigA.
- HigB targets specific mRNAs, including an efflux pump, affecting cell viability and cell cycle progression.
Conclusions:
- Bacterial toxin-antitoxin systems can exhibit dynamic regulatory roles, influencing both stress adaptation and fundamental cellular processes like the cell cycle.
- Understanding TAS target selectivity is key to deciphering their integration into complex bacterial regulatory networks.
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