Arrested protein synthesis increases persister-like cell formation

Brian W. Kwan, John A. Valenta, Michael J. Benedik, Thomas Keith Wood

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Biofilms are associated with a wide variety of bacterial infections and pose a serious problem in clinical medicine due to their inherent resilience to antibiotic treatment. Within biofilms, persister cells comprise a small bacterial subpopulation that exhibits multidrug tolerance to antibiotics without undergoing genetic change. The low frequency of persister cell formation makes it difficult to isolate and study persisters, and bacterial persistence is often attributed to a quiescent metabolic state induced by toxins that are regulated through toxin-antitoxin systems. Here we mimic toxins via chemical pretreatments to induce high levels of persistence (10 to 100%) from an initial population of 0.01%. Pretreatment of Escherichia coli with (i) rifampin, which halts transcription, (ii) tetracycline, which halts translation, and (iii) carbonyl cyanide m-chlorophenylhydrazone, which halts ATP synthesis, all increased persistence dramatically. Using these compounds, we demonstrate that bacterial persistence results from halted protein synthesis and from environmental cues.

Original languageEnglish (US)
Pages (from-to)1468-1473
Number of pages6
JournalAntimicrobial agents and chemotherapy
Volume57
Issue number3
DOIs
StatePublished - Mar 1 2013

Fingerprint

Biofilms
Anti-Bacterial Agents
Antitoxins
Clinical Medicine
Rifampin
Tetracycline
Bacterial Infections
Cues
Proteins
Adenosine Triphosphate
Escherichia coli
Population
carbonyl 3-chlorophenylhydrazone
mesoxalonitrile

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Kwan, Brian W. ; Valenta, John A. ; Benedik, Michael J. ; Wood, Thomas Keith. / Arrested protein synthesis increases persister-like cell formation. In: Antimicrobial agents and chemotherapy. 2013 ; Vol. 57, No. 3. pp. 1468-1473.
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Arrested protein synthesis increases persister-like cell formation. / Kwan, Brian W.; Valenta, John A.; Benedik, Michael J.; Wood, Thomas Keith.

In: Antimicrobial agents and chemotherapy, Vol. 57, No. 3, 01.03.2013, p. 1468-1473.

Research output: Contribution to journalArticle

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AB - Biofilms are associated with a wide variety of bacterial infections and pose a serious problem in clinical medicine due to their inherent resilience to antibiotic treatment. Within biofilms, persister cells comprise a small bacterial subpopulation that exhibits multidrug tolerance to antibiotics without undergoing genetic change. The low frequency of persister cell formation makes it difficult to isolate and study persisters, and bacterial persistence is often attributed to a quiescent metabolic state induced by toxins that are regulated through toxin-antitoxin systems. Here we mimic toxins via chemical pretreatments to induce high levels of persistence (10 to 100%) from an initial population of 0.01%. Pretreatment of Escherichia coli with (i) rifampin, which halts transcription, (ii) tetracycline, which halts translation, and (iii) carbonyl cyanide m-chlorophenylhydrazone, which halts ATP synthesis, all increased persistence dramatically. Using these compounds, we demonstrate that bacterial persistence results from halted protein synthesis and from environmental cues.

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