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Arrested protein synthesis increases persister-like cell formation

Brian W Kwan1, John A Valenta, Michael J Benedik

  • 1Department of Chemical Engineering, Pennsylvania State University, University Park, PA, USA.

Antimicrobial Agents and Chemotherapy
|January 9, 2013
PubMed

Insights

Chemicals that halt protein synthesis or ATP production can dramatically increase bacterial persistence. This finding helps understand how persister cells survive antibiotic treatments in biofilms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Bacterial biofilms are linked to persistent infections and are notoriously resistant to antibiotics.
  • Persister cells within biofilms are a small subpopulation exhibiting multidrug tolerance without genetic mutation.
  • Toxin-antitoxin systems and quiescent states are thought to regulate persister cell formation.

Purpose of the Study:

  • To investigate methods for inducing high levels of bacterial persistence.
  • To elucidate the mechanisms underlying persister cell formation and survival.

Main Methods:

  • Escherichia coli cultures were pretreated with specific chemical agents.
  • Chemicals used included rifampin (halts transcription), tetracycline (halts translation), and carbonyl cyanide m-chlorophenylhydrazone (halts ATP synthesis).
  • Persistence levels were quantified following chemical pretreatment.

Main Results:

  • Pretreatment with rifampin, tetracycline, or carbonyl cyanide m-chlorophenylhydrazone significantly increased persister cell formation from 0.01% to 10-100%.
  • Bacterial persistence was demonstrated to be a result of halted protein synthesis.
  • Environmental cues were also identified as contributing factors to persistence.

Conclusions:

  • Halted protein synthesis is a key driver of bacterial persistence.
  • Chemical induction offers a viable method to study high-frequency persister cells.
  • Understanding persistence mechanisms is crucial for developing effective treatments against biofilm infections.

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