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.
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)