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

8. Persistence V.S. Resistance

9. Persistence V.S. Resistance

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)