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Bacterial Persistence
   Instructor: Dr. Wu, Jia-Feng

         Chu, Yung-Tsai
          2011.01.02
Outline
 What is Bacterial Persistence
 Possible Mechanism
 Comparison with Antibiotics Resistance
 Importance
 Take Home Message
Bacterial Persistence
   a state in which a sub-population of dormant
    cells, or ‘persisters’, tolerates antibiotic
    treatment
       A dormant cell has a global slowdown of metabolic
        processes and does not divide
Discovery in 1944
   Joseph BIGGER demonstrated that penicillin
    can kill merely 99% of the bacteria.

   The remaining 1% of the bacteria were
    persisters.

   When these persisters were cultured to fresh
    media, they regained susceptibility to antibiotics.
Implication
   1. Certain sub-population can persist under the
    antibiotic treatment.

   2. They are still susceptible to the antibiotics.

   These cells have not genetically acquired
    antibiotic resistance.
Mechanism



  Growth       Dormant
 (Dividing)   (Persister)
Current Hypothesis
   Toxin-antitoxin module
       the toxin is a protein that inhibits an important cellular
        function
Persistence V.S. Resistance
Persistence V.S. Resistance
Importance
 Multidrug -Tolerance
 Biofilms
 Chronic Infection
       Treponema pallidum (syphilis)
       M. tuberculosis (TB)
   Association with antibiotics resistance
Take Home Message
   The entrance of cells into a dormant, persistent
    state is largely responsible for the multidrug
    tolerance of infections

   Persisters are likely to be responsible for
    Multidrug tolerance of biofilms and latent
    (chronic) diseases, such as TB
Reference
   Bigger, J. W. Treatment of staphylococcal infections with penicillin. Lancet 497–500
    (1944).
   Allison KR, Brynildsen MP, Collins JJ. Metabolite-enabled eradication of bacterial
    persisters by aminoglycosides.Nature. 2011 May 12;473(7346):216-20.
   Lewis K. Persister cells, dormancy and infectious disease.Nat Rev Microbiol. 2007
    Jan;5(1):48-56. Epub 2006 Dec 4.
   Levin BR, Rozen DE. Non-inherited antibiotic resistance.Nat Rev Microbiol. 2006
    Jul;4(7):556-62.
   Kussell, E., Kishony, R., Balaban, N. Q. & Leibler, S. Bacterial persistence: a model
    of survival in changing environments. Genetics 169, 1807–1814 (2005).
   Buts L, Lah J, Dao-Thi MH, Wyns L, Loris R. Toxin-antitoxin modules as bacterial
    metabolic stress managers. Trends Biochem Sci. 2005 Dec;30(12):672-9. Epub 2005
    Oct 28.
   Zhang Y. Mechanisms of Antibiotic Resistance in the Microbial World.
    (http://www.moleculartb.org/gb/pdf/transcriptions/11_YZhang.pdf)

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Bacterial persistence

  • 1. Bacterial Persistence Instructor: Dr. Wu, Jia-Feng Chu, Yung-Tsai 2011.01.02
  • 2. Outline  What is Bacterial Persistence  Possible Mechanism  Comparison with Antibiotics Resistance  Importance  Take Home Message
  • 3. Bacterial Persistence  a state in which a sub-population of dormant cells, or ‘persisters’, tolerates antibiotic treatment  A dormant cell has a global slowdown of metabolic processes and does not divide
  • 4. Discovery in 1944  Joseph BIGGER demonstrated that penicillin can kill merely 99% of the bacteria.  The remaining 1% of the bacteria were persisters.  When these persisters were cultured to fresh media, they regained susceptibility to antibiotics.
  • 5. Implication  1. Certain sub-population can persist under the antibiotic treatment.  2. They are still susceptible to the antibiotics.  These cells have not genetically acquired antibiotic resistance.
  • 6. Mechanism Growth Dormant (Dividing) (Persister)
  • 7. Current Hypothesis  Toxin-antitoxin module  the toxin is a protein that inhibits an important cellular function
  • 10. Importance  Multidrug -Tolerance  Biofilms  Chronic Infection  Treponema pallidum (syphilis)  M. tuberculosis (TB)  Association with antibiotics resistance
  • 11. Take Home Message  The entrance of cells into a dormant, persistent state is largely responsible for the multidrug tolerance of infections  Persisters are likely to be responsible for Multidrug tolerance of biofilms and latent (chronic) diseases, such as TB
  • 12. Reference  Bigger, J. W. Treatment of staphylococcal infections with penicillin. Lancet 497–500 (1944).  Allison KR, Brynildsen MP, Collins JJ. Metabolite-enabled eradication of bacterial persisters by aminoglycosides.Nature. 2011 May 12;473(7346):216-20.  Lewis K. Persister cells, dormancy and infectious disease.Nat Rev Microbiol. 2007 Jan;5(1):48-56. Epub 2006 Dec 4.  Levin BR, Rozen DE. Non-inherited antibiotic resistance.Nat Rev Microbiol. 2006 Jul;4(7):556-62.  Kussell, E., Kishony, R., Balaban, N. Q. & Leibler, S. Bacterial persistence: a model of survival in changing environments. Genetics 169, 1807–1814 (2005).  Buts L, Lah J, Dao-Thi MH, Wyns L, Loris R. Toxin-antitoxin modules as bacterial metabolic stress managers. Trends Biochem Sci. 2005 Dec;30(12):672-9. Epub 2005 Oct 28.  Zhang Y. Mechanisms of Antibiotic Resistance in the Microbial World. (http://www.moleculartb.org/gb/pdf/transcriptions/11_YZhang.pdf)