Wednesday, June 1, 2011

Persister bacteria and their role in chronic infections- a brief review


Complete sterilization of a bacterial culture is expected when an antibiotic-sensitive bacterial population is treated with optimal concentrations of antibiotics. However, Joseph Bigger in 1944 noticed that penicillin could not sterilize a Staphylococcal culture completely even in the absence of a penicillin-resistant population. While most of the bacteria were killed by penicillin, Bigger noticed that a small subpopulation somehow survived which were neither killed nor grown in the presence of antibiotics. Upon removal of penicillin, the survivors grew abundantly just like the parent population. They were as sensitive as the parent population to the bactericidal action of the antibiotic but again left a small percentage of survivors. It is argued that the survival of this small subpopulation of persisters in the presence of antibiotics is not due to antibiotic resistance, but rather to their ability to undergo a phenotypic shift by remaining in a dormant, non-dividing state that enable them to survive the lethal actions of antibiotics.

Some of the properties of persisters are
-they are not induced by antibiotics nor are they mutants.
-their formation depends on the growth stage of bacteria but they are not cells at a particular stage in the cell cycle. During the stationary phase, the number of persisters increases.
-they represent a very small subpopulation of less than 1% of the total population.
-persisters are tolerant to antibiotics and are neither killed nor grown in the presence of antibiotics. They exhibit increased MBC (minimum bactericidal concentration) but show almost the same MIC (minimum inhibitory concentration) as the wild type
-they are pre-formed rather than being generated during the antibiotic treatment. However, an inducible mechanism of persister formation mediated by SOS response has been recently reported
-the phenotypic shift of persisters is reported to be under genetic control since overexpression of genes such as hipA, relE, mazF results in high number of persisters.

Isolating persisters is difficult because of their low number in the presence of antibiotics and because of their ability to undergo phenotypic shift upon the removal of the antibiotic. However, high persister (hiP) mutants of E. coli, first isolated by Moyed and Bertrand (1983), can be used to obtain large number of persisters.

Persisters are implicated in chronic and recurrent infections as they can survive antibiotic treatment and re-grow later on the removal of antibiotics. Similarly, they are implicated in biofilm-associated infections. Persisters in the biofilm may be more important than the planktonic cells in recurrent infections (Lewis 2007). Antibiotic treatment may kill majority of the biofilm and planktonic cells but may leave the persisters intact. Whereas the planktonic persister cells may be removed by the immune system, the biofilm persisters may be protected by the matrix from the immune cells. Once the antibiotic is removed, those persisters in the biofilm may start to grow and repopulate the biofilm, which may later release some planktonic cells causing recurrent infections.



Lewis, K. (2007). Persister cells, dormancy and infectious diseases. Nat Rev Microbiol. 5(1): 48-56.


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