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ComGA-RelA interaction and persistence in the Bacillus subtilis K-state.

Jeanette Hahn1, Andrew W Tanner1, Valerie J Carabetta1

  • 1Public Health Research Institute Center of New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ, 07103, USA.

Molecular Microbiology
|April 23, 2015
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Bacillus subtilis K-state cells exhibit arrested growth and antibiotic tolerance due to ComGA protein interactions. This growth arrest, linked to (p)ppGpp levels, may be a bet-hedging strategy for bacterial survival.

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Area of Science:

  • Microbiology
  • Bacterial Physiology
  • Molecular Biology

Background:

  • Bacillus subtilis exhibits a bistable K-state with distinct transformability and growth arrest phenotypes.
  • Growth arrest involves failure in replisome assembly and reduced rRNA synthesis, linked to the ComGA protein.
  • ComGA is crucial for DNA binding, transformation pilus assembly, and DNA transport.

Purpose of the Study:

  • To elucidate the molecular mechanism behind ComGA-mediated growth arrest in Bacillus subtilis.
  • To investigate the role of the alarmone (p)ppGpp in the K-state growth arrest.
  • To explore the adaptive significance of bistable K-state expression as a bet-hedging strategy.

Main Methods:

  • Investigated protein-protein interactions using ComGA and RelA.
  • Analyzed rRNA synthesis rates in wild-type and mutant strains.
  • Assessed growth rates and antibiotic tolerance in K-state cells.
  • Utilized genetic manipulation to create strains with altered (p)ppGpp synthesis.

Main Results:

  • Discovered a physical interaction between ComGA and RelA.
  • ComGA-dependent inhibition of rRNA synthesis is significantly reduced in strains lacking (p)ppGpp synthesis.
  • ComGA interaction with RelA appears to prevent (p)ppGpp hydrolysis, maintaining the non-growing state.
  • Some K-state cells display antibiotic tolerance, a characteristic of type 1 persistence.

Conclusions:

  • ComGA-RelA interaction and subsequent (p)ppGpp accumulation likely cause K-state growth arrest.
  • Bistable expression of transformability and growth arrest may represent bet-hedging adaptations for environmental fitness.
  • These adaptations potentially enhance Bacillus subtilis survival in fluctuating environments, such as soil.