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Proteolytic Queues at ClpXP Increase Antibiotic Tolerance.

Heather S Deter1, Alawiah H Abualrahi1, Prajakta Jadhav1

  • 1Department of Biology and Microbiology , South Dakota State University , Brookings , South Dakota 57006 , United States.

ACS Synthetic Biology
|December 21, 2019
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Summary

Protease queueing significantly boosts bacterial antibiotic tolerance, enhancing survival against ampicillin and ciprofloxacin treatments. This finding offers a new way to study bacterial tolerance without genetic manipulation.

Keywords:
ClpXPantibiotic resistanceantibiotic tolerancepersistenceproteasequeueingsynthetic biology

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Systems Biology

Background:

  • Antibiotic tolerance is a major challenge in treating bacterial infections, contributing to antibiotic resistance.
  • Proteases, enzymes that degrade proteins, are implicated in the survival of bacterial subpopulations like persisters.
  • Understanding the mechanisms of antibiotic tolerance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of proteases, specifically proteolytic queueing, in bacterial antibiotic tolerance.
  • To differentiate antibiotic tolerance from antibiotic persistence using computational and experimental methods.
  • To establish proteolytic queueing as a method for studying protease function in bacterial tolerance.

Main Methods:

  • Utilized queueing theory, computational modeling, and synthetic biology approaches.
  • Examined antibiotic tolerance in *E. coli* populations treated with ampicillin and ciprofloxacin.
  • Distinguished between antibiotic tolerance (short-term survival) and persistence (long-term survival/population decay).

Main Results:

  • Proteolytic queueing at the ClpXP protease increased antibiotic tolerance by approximately 80-fold for ampicillin and 60-fold for ciprofloxacin in *E. coli*.
  • No significant effect of proteolytic queueing was observed on antibiotic persistence.
  • Demonstrated that proteolytic queueing is a viable method to study protease activity in bacterial tolerance.

Conclusions:

  • Proteolytic queueing is a key factor in enhancing short-term bacterial survival under antibiotic stress.
  • This phenomenon provides a novel approach to investigate protease function in antibiotic tolerance without genetic modifications.
  • The findings contribute to a better understanding of bacterial survival strategies and may inform new therapeutic interventions.