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 (Dividing)

Dormant (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)