Persister cells
Persister cells are subpopulations of cells that resist treatment, and become antimicrobial tolerant by changing to a state of
History
Recognition of bacterial persister cells dates back to 1944 when
Relevance to chronic infections
Antimicrobial tolerance is achieved by a small subpopulation of microbial cells termed persisters.
The bacteria species Listeria monocytogenes, the main causal agent of listeriosis, has been shown to demonstrate persistence during infection in hepatocyte and trophoblast cells. The usual active lifestyle can change and the bacteria can remain in intracellular vacuoles entering into a slow non-growing state of persistence thus promoting their survival from antibiotics.[12]
Fungal persister cells are a common cause of recurring infections due to Candida albicans a common biofilm infection of implants.[5]
Medical importance
Antibiotic tolerance poses medically important challenges. It is largely responsible for the inability to eradicate bacterial infections with antibiotic treatment. Persister cells are highly enriched in biofilms, and this makes biofilm-related diseases difficult to treat. Examples are chronic infections of implanted medical devices such as catheters and artificial joints, urinary tract infections, middle ear infections and fatal lung disease.[13]
Resistance vs tolerance
Unlike
Molecular mechanisms
The molecular mechanisms that underlie persister cell formation, and antimicrobial tolerance are largely unknown.
Although tolerance is widely considered a passive state, there is evidence indicating it can be an energy-dependent process.[20] Persister cells in E. coli can transport intracellular accumulations antibiotic using an energy requiring efflux pump called TolC.[21]
A persister subpopulation has also been demonstrated in budding yeast Saccharomyces cerevisiae. Yeast persisters are triggered in a small subset of unperturbed exponentially growing cells by spontaneously occurring DNA damage, which leads to the activation of a general stress response and protection against a range of harsh drug and stress environments. As a result of the DNA damage, yeast persisters are also enriched for random genetic mutations that occurred prior to the stress, and are unrelated to the stress survival.[22]
In response to antifungals, fungal persister cells activate stress-response pathways, and two stress-protective molecules – glycogen, and trehalose accumulate in large amounts.[5]
Potential treatment
A study has shown that adding certain
Phage therapy, where applicable, entirely circumvents antibiotic tolerance.[24][25]
See also
References
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External links
- "Persister cells and mode of action of HipA". Archived from the original on March 28, 2010.