The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Persister Cells: Molecular Mechanisms Related to Antibiotic Tolerance
Abstract
It is a given that new antibiotics are needed to combat drug-resistant pathogens. However, this is only a part of the need-we actually never had antibiotics capable of eradicating an infection. All pathogens produce a small subpopulation of dormant persister cells that are highly tolerant to killing by antibiotics. Once an antibiotic concentration drops, surviving persisters re-establish the population, causing a relapsing chronic infection. Persisters are especially significant when the pathogen is shielded from the immune system by biofilms, or in sites where the immune components are limited-in the nervous system, the stomach, or inside macrophages.Antibiotic treatment during a prolonged chronic infection of P. aeruginosa in the lungs of patients with cystic fibrosis selects for high-persister (hip) mutants. Similarly, treatment of oral thrush infection selects for hip mutants of C. albicans. These observations suggest a direct causality between persisters and recalcitrance of the disease. It appears that tolerance of persisters plays a leading role in chronic infections, while resistance is the leading cause of recalcitrance to therapy in acute infections. Studies of persister formation in E. coli show that mechanisms of dormancy are highly redundant. Isolation of persisters produced a transcriptome which suggests a dormant phenotype characterized by downregulation of energy-producing and biosynthetic functions. Toxin-antitoxin modules represent a major mechanism of persister formation. The RelE toxin causes dormancy by cleaving mRNA; the HipA toxin inhibits translation by phosphorylating elongation factor Ef-Tu, and the TisB toxin forms a membrane pore, leading to a decrease in pmf and ATP.
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“Indeed, such a strategy parallels the formation of antibiotic tolerant persister cells (75, 76).”
From Staphylococcus aureus Adapts to Oxidative Stress by Producing H 2 O 2 -Resistant Small-Colony Variants via the SOS Response (2015) · cites this paper as [76]
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Cites
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Self-citationTOR, a Central Controller of Cell Growth
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Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis
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Smith, E. E., Buckley, D. G., Wu, Z., Saenphimmachak, C., Hoffman, L. R., D’Argenio, D. A., Miller, S. I., Ramsey, B. W., Speert, D. P., Moskowitz, S. M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602138103 · Cited by 1,319
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Biofilms: The Microbial “Protective Clothing” in Extreme Environments
Yin, W., Wang, Y., Liu, L., & He, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143423 · Cited by 1,017
Antibiotic resistance and persistence—implications for human health and treatment perspectives
Huemer, M., Mairpady Shambat, S., Brugger, S. D., & Zinkernagel, A. S. (2020) · The EMBO Reports · doi:10.15252/embr.202051034 · Cited by 850
Biofilm-specific antibiotic tolerance and resistance
Olsen, I. (2015) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-015-2323-z · Cited by 742
Bacterial Contribution in Chronicity of Wounds
Rahim, K., Saleha, S., Zhu, X., Huo, L., Basit, A., & Franco, O. L. (2016) · Microbial Ecology · doi:10.1007/s00248-016-0867-9 · Cited by 457
The Impact of Dental Implant Surface Modifications on Osseointegration and Biofilm Formation
Kligman, S., Ren, Z. F., Chung, C., Perillo, M. A., Chang, Y., Koo, H., Zheng, Z. S., & Li, C. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10081641 · Cited by 392
Metadata
- Authors
- Lewis, K.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Lewis, Kim
- ORCID
- Lewis, Kim
- Venue
- Handbook of Experimental Pharmacology
- Publisher
- Springer Berlin Heidelberg
- Published
- 2012
- Issue
- 211
- Pages
- 121-133
- ISSN
- 0171-2004 (ISSN-L)
- 1865-0325
- OpenAlex
- W135230180
- Cited by
- 217
- References
- 61
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 8 · 2023: 14 · 2022: 13 · 2021: 13 · 2020: 29 · 2019: 24 · 2018: 16 · 2017: 19 · 2016: 17 · 2015: 18 · 2014: 11 · 2013: 14 · 2012: 1
- FWCI
- 34.62
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- Locations
- Handbook of experimental pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- persister cells, antibiotic tolerance, bacterial dormancy, toxin-antitoxin systems, chronic infection, biofilm, cystic fibrosis, Pseudomonas aeruginosa, Candida albicans, oral candidiasis, Escherichia coli, efflux pumps, membrane potential, infection relapse
- MeSH terms
- Candida albicans, Cystic Fibrosis, Drug Resistance, Microbial, Escherichia coli, Humans, Pseudomonas aeruginosa
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