Persisters are defined as a small subpopulation of bacteria, constituting less than 1% of the total population, that are either dormant or slow growing and capable of evading death by antibiotics by exhibiting transient multi-drug tolerance.
Recently it was shown that, following exposure to levofloxacin and vancomycin, Staphylococcus epidermidis RP62a biofilms contained 28% and 94% persisters respectively (Shapiro et al. 2011). Are they persisters, by definition? Similarly, following exposure to the above antibiotics, the number of planktonic persister cells was less than 1% of the total population during the log phase, but produced almost the same number of cells as the antibiotic-untreated control group during stationary phase. Are these cells persisters? As per Lewis (2007), the maximum number of persisters is ~1% of cells which are produced during the stationary phase. “examination of the rate of E. coli persister-cell formation over time showed that few of these cells are formed in early exponential phase, followed by a sharp increase in persister-cell formation in mid-exponential phase, reaching a maximum of ~1% of cells forming persisters in the non-growing stationary phase”.
Low number of persisters is considered as a barrier to the discovery of persister genes (Lewis 2007). However, if persisters constitute more than 90% of the population (Shapiro et al. 2011), why it is difficult to isolate persisters and study persister genes? Similarly, why researchers have to depend on expensive and complicated microfluidic devices to isolate persisters (Balaban et al. 2004)?
The reason for the discrepancy is that the definition for persisters is based on particular experimental condition only and that the researchers have ‘misused’ the term persisters for any type of survivors following antibiotic treatment. As for another example, Harrison et al. (2005) found that 24 h of exposure of E. coli JM109 to antibiotics did not produce any survivors whereas a short incubation for 2 h resulted in many survivors. Similarly, they found that the highly tolerant E. coli JM109 survivors could be eradicated by metal oxyanions by 24 h exposure. Are the survivors after 2 h exposure to antibiotics or metal oxyanions persisters?
Next- Inoculum effect- a factor affecting the number of survivors
Shapiro et al. (2011). Evidence for persisters in Staphylococcus epidermidis RP62a planktonic cultures and biofilms. J. Med. Micro. DOI: 10.1099/jmm.0.026013-0
Harrison et al. (2005). Persister cells mediate tolerance to metal oxyanions in Escherichia coli. Microbiology 151: 3181-3195.
Lewis, K. (2007). Persister cells, dormancy and infectious diseases. Nat Rev Microbiol. 5(1): 48-56.
Balaban et al. (2004). Bacterial persistence as a phenotypic switch. Science 305 (5690): 1622-1625.
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