If persisters are non-mutants, are hip mutants persisters?

Persisters are defined as non-mutants that form a small subpopulation of bacteria exhibiting transient antibiotic tolerance. i.e. in the presence of antibiotics, they are tolerant to the bactericidal activity of antibiotics, but once the antibiotics are removed, they again become sensitive to antibiotics. Researchers have studied a number of hip (high persister) mutants and showed that the hip mutants produce a high frequency of persisters. Example includes the most commonly studied hipA mutants. In addition, other hip mutants whose genetic background is not known, is also reported. For example, Lafleur et al. (2010) suggested that the fifteen hip isolates they had identified had an underlying genetic change. Similarly, Mulcahy et al. (2010) found that the late isolates of P.aeroginosa from cystic fibrosis patients that showed a 100-fold increase in persister levels carried a large number of mutations including mutS and mexZ.

If persisters are non-mutants, can those mutants be considered as persisters?

Some explanations are available..

“The formation of hip mutants may be a general feature of recalcitrant fungal infections, although it is likely that persisters from both wild-type strains and hip mutants contribute to drug tolerance and the survival of the pathogen.” (Lafleur et al. 2010)

“While the persister state is a temporary one for a bacterial cell, the frequency with which cells enter this temporary state can be increased by mutations. A mutant that has an increased frequency of persister formation then is a hip mutant. Once these mutants are selected, the population stably forms more persisters than the wild-type strain from which it was derived.” (Mulcahy et al. 2010)

Can we consider the persisters from both wild type bacteria and hip mutants the same even though the latter has an underlying genetic change? If they are the same, why persisters are defined as non-mutants?

Lafleur et al. (2010). Patients with long-term oral carriage harbor high-persister mutants of Candida albicans. Antimicrob Agents Chemother 54(1), 39-44.

Mulcahy et al. (2010). Emergence of Pseudomonas aeroginosa strains producing high levels of persister cells in patients with cystic fibrosis. Journal of Bacteriology 192(23): 6191-6199.