Researchers have considered any bacteria that survive antibiotic therapy as persisters. Persisters, thus include
1. a small subpopulation of bacteria that survive antibiotic treatment in vitro
2. bacteria in biofilms, not killed by antibiotics
3. stationary phase bacteria, tolerant to antibiotics
4. mutant bacteria including hipA mutants
5. bacteria surviving in chronic and recurrent infections in spite of antibiotic therapy
Even though they are all termed persisters, the reason why they survive may be different for each of the above cases and some of those persisters (as demonstrated in many experiments) may not have any clinical significance.
Similarly, some of the statements on persisters and their phenotypic shift are contradictory
1. Even though they are termed non-mutants, majority of persisters have a genetic background (refer July 18 blogpost)
2. isolation of persisters is considered difficult as they constitute less than 1% of the population. However, persisters may form upto 94% in biofilms and hence isolation should not be difficult (June 3)
3. Even though hipA is the best studied persister gene, it is not present in the genomes of M. tuberculosis, P. aeruginosa or S. aureus, the organisms responsible for many chronic infections (June 23 and 27)
4. Moreover, hipA mutants have not been isolated either in vitro or in vivo for decades (July 16)
5. Even though researchers argue that MBC do not take into account of persisters, they still use MBC values in determining the activities of antimicrobial agents against persisters (June 26)
6. Many of the treatment strategies against persisters are questionable (June 10, 13, 15 and 28)
It is known that chronic infections and biofilm-associated infections are difficult to treat with conventional antibiotic therapy. However, using this knowledge, researchers have created an in vitro illusion through retrospective thinking to demonstrate that such infections are caused by a phenotypic shift of persisters.
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