The DOI matches its Crossref record; 76 of the 77 references it cites were found in a registry or an index.
Persister cells, dormancy and infectious disease
Abstract
Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.
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“Persistence is always linked to cell dormancy, a state in which the cellular metabolism temporarily ceases [111,123,124].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [124]
In the citing paper
“In contrast, resistance is linked to specific molecular mechanisms and can be stably inherited by progeny [15,17–19].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [18]
In the citing paper
“Thirdly, antifungal persistence is non-heritable, although the progeny of persisters may still divide into persistent subpopulations and non-persistent subpopulations.”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [18]
In the citing paper
“It has been well studied that dormant state reduces the exposure of antibiotic targets and helps bacterial cells tolerate a variety of antibiotics, a process linked to the toxin-antitoxin system [18,54].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [18]
Citations
Cites
Bacterial biofilms: from the Natural environment to infectious diseases
Hall‐Stoodley, L., Costerton, J. W., & Stoodley, P. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro821 · Cited by 7,133
Antibacterial resistance worldwide: causes, challenges and responses
Levy, S. B., & Marshall, B. M. (2004) · Nature Medicine · doi:10.1038/nm1145 · Cited by 4,152
Bacterial Persistence as a Phenotypic Switch
Balaban, N. Q., Merrin, J., Chait, R., Kowalik, L., & Leibler, S. (2004) · Science · doi:10.1126/science.1099390 · Cited by 2,952
Stochasticity in gene expression: from theories to phenotypes
Kærn, M., Elston, T. C., Blake, W. J., & Collins, J. J. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1615 · Cited by 2,318
Chemotaxis in Escherichia coli analysed by Three-dimensional Tracking
Berg, H. C., & Brown, D. A. (1972) · Nature · doi:10.1038/239500a0 · Cited by 2,239
Lewis, K. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.4.999-1007.2001 · Cited by 2,005
Self-citationTOR, a Central Controller of Cell Growth
Schmelzle, T., & Hall, M. N. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 1,914
Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms
Singh, P. K., Schaefer, A. L., Parsek, M. R., Moninger, T. O., Welsh, M. J., & Greenberg, E. P. (2000) · Nature · doi:10.1038/35037627 · Cited by 1,519
Staley, J. T., & Konopka, A. E. (1985) · Annual Review of Microbiology · doi:10.1146/annurev.mi.39.100185.001541 · Cited by 1,512
Isolating "Uncultivable" Microorganisms in Pure Culture in a Simulated Natural Environment
Kaeberlein, T., Lewis, K., & Epstein, S. S. (2002) · Science · doi:10.1126/science.1070633 · Cited by 1,258
Self-citationGenome Streamlining in a Cosmopolitan Oceanic Bacterium
Giovannoni, S. J., Tripp, H. J., Givan, S. A., Podar, M., Vergin, K. L., Baptista, D., Bibbs, L., Eads, J. R., Richardson, T. H., Noordewier, M. O., et al. (2005) · Science · doi:10.1126/science.1114057 · Cited by 1,224
Designing surfaces that kill bacteria on contact
Tiller, J. C., Liao, C.-J., Lewis, K., & Klibanov, A. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111143098 · Cited by 1,196
Self-citationTREATMENT OF STAPHYLOCOCCAL INFECTIONS WITH PENICILLIN BY INTERMITTENT STERILISATION
Bigger, J. (1944) · The Lancet · doi:10.1016/s0140-6736(00)74210-3 · Cited by 1,164
Persister cells and tolerance to antimicrobials
Keren, I., Kaldalu, N., Spoering, A. L., Wang, Y., & Lewis, K. (2003) · FEMS Microbiology Letters · doi:10.1016/s0378-1097(03)00856-5 · Cited by 1,094
Self-citationProkaryotic toxin–antitoxin stress response loci
Gerdes, K., Christensen, S. K., & Løbner‐Olesen, A. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1147 · Cited by 1,033
Cultivation of the ubiquitous SAR11 marine bacterioplankton clade
Rappé, M. S., Connon, S. A., Vergin, K. L., & Giovannoni, S. J. (2002) · Nature · doi:10.1038/nature00917 · Cited by 1,020
Spoering, A. L., & Lewis, K. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.23.6746-6751.2001 · Cited by 907
Self-citationToxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes
Pandey, D. P. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki201 · Cited by 896
Specialized Persister Cells and the Mechanism of Multidrug Tolerance in Escherichia coli
Keren, I., Shah, D., Spoering, A. L., Kaldalu, N., & Lewis, K. (2004) · Journal of Bacteriology · doi:10.1128/jb.186.24.8172-8180.2004 · Cited by 848
Self-citationZengler, K., Toledo, G., Rappé, M., Elkins, J., Mathur, E. J., Short, J. M., & Keller, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252630999 · Cited by 796
Connon, S. A., & Giovannoni, S. J. (2002) · Applied and Environmental Microbiology · doi:10.1128/aem.68.8.3878-3885.2002 · Cited by 742
Dubnau, D. A., & Losick, R. M. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05249.x · Cited by 729
Unique type of plasmid maintenance function: postsegregational killing of plasmid-free cells.
Gerdes, K., Rasmussen, P. B., & Molin, S. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.10.3116 · Cited by 677
Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa
Li, X. Z., Nikaido, H., & Poole, K. (1995) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.39.9.1948 · Cited by 660
Moyed, H. S., & Bertrand, K. P. (1983) · Journal of Bacteriology · doi:10.1128/jb.155.2.768-775.1983 · Cited by 641
Vuong, C., Voyich, J. M., Fischer, E. R., Braughton, K. R., Whitney, A. R., DeLeo, F. R., & Otto, M. J. (2004) · Cellular Microbiology · doi:10.1046/j.1462-5822.2004.00367.x · Cited by 633
Persisters: a distinct physiological state of E. coli
Khodursky, A. B., Zhang, Z., Devang, S., Kaldalu, N., Kurg, K., & Lewis, K. (2006) · Digital Repository Service (Northeastern University) · doi:10.1186/1471-2180-6-53 · Cited by 630
Self-citationLewis, K. (2000) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.64.3.503-514.2000 · Cited by 614
Self-citationToxins-Antitoxins: Plasmid Maintenance, Programmed Cell Death, and Cell Cycle Arrest
Hayes, F. (2003) · Science · doi:10.1126/science.1088157 · Cited by 586
Cannibalism by sporulating bacteria.
González-Pastor, J. E., Hobbs, E. C., & Losick, R. (2003) · Science · doi:10.1126/science.1086462 · Cited by 579
Mechanism of plasmid-mediated quinolone resistance
Tran, J. H., & Jacoby, G. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082092899 · Cited by 578
M. tuberculosis persistence, latency, and drug tolerance
Gomez, J. E., & McKinney, J. D. (2003) · Tuberculosis · doi:10.1016/j.tube.2003.08.003 · Cited by 546
Non-inherited antibiotic resistance
Levin, B. R., & Rozen, D. E. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1445 · Cited by 546
Permanent, nonleaching antibacterial surfaces: 1. Synthesis by atom transfer radical polymerization
Lee, S. B., Koepsel, R. R., Morley, S. W., Matyjaszewski, K., Sun, Y., & Russell, A. J. (2004) · Biomacromolecules · doi:10.1021/bm034352k · Cited by 545
Microbial Cell Individuality and the Underlying Sources of Heterogeneity
Avery, S. V. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1460 · Cited by 521
Candida albicans Biofilms Produce Antifungal-Tolerant Persister Cells
LaFleur, M. D., Kumamoto, C. A., & Lewis, K. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00684-06 · Cited by 521
Self-citationA Dose-Response Study of Antibiotic Resistance in Pseudomonas aeruginosa Biofilms
Brooun, A., Liu, S., & Lewis, K. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.3.640-646.2000 · Cited by 474
Self-citationFrom molecular noise to behavioural variability in a single bacterium
Korobkova, E. A., Emonet, T., Vilar, J. M. G., Shimizu, T. S., & Cluzel, P. (2004) · Nature · doi:10.1038/nature02404 · Cited by 455
Human Leukocytes Adhere to, Penetrate, and Respond to Staphylococcus aureus Biofilms
Leid, J. G., Shirtliff, M. E., Costerton, J. W., & Stoodley, A. P. (2002) · Infection and Immunity · doi:10.1128/iai.70.11.6339-6345.2002 · Cited by 406
Christensen, S. K., Pedersen, K. B., Hansen, F. G., & Gerdes, K. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00922-7 · Cited by 380
Jesaitis, A. J., Franklin, M. J., Berglund, D. L., Sasaki, M., Lord, C. I., Bleazard, J. B., Duffy, J. E., Beyenal, H., & Lewandowski, Z. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.8.4329 · Cited by 373
Pedersen, K. B., Christensen, S. K., & Gerdes, K. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03027.x · Cited by 360
Christensen, S. K., & Gerdes, K. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03512.x · Cited by 338
Milović, N. M., Wang, J., Lewis, K., & Klibanov, A. M. (2005) · Biotechnology and Bioengineering · doi:10.1002/bit.20454 · Cited by 322
Self-citationSurpassing nature: rational design of sterile-surface materials
Lewis, K., & Klibanov, A. M. (2005) · Trends in biotechnology · doi:10.1016/j.tibtech.2005.05.004 · Cited by 310
Self-citationLin, J., Qiu, S., Lewis, K., & Klibanov, A. M. (2003) · Biotechnology and Bioengineering · doi:10.1002/bit.10651 · Cited by 300
Self-citationA Fluoroquinolone Resistance Protein from Mycobacterium tuberculosis That Mimics DNA
Hegde, S. S., Vetting, M. W., Roderick, S. L., Mitchenall, L. A., Maxwell, A., Takiff, H. E., & Blanchard, J. S. (2005) · Science · doi:10.1126/science.1110699 · Cited by 299
Davis, B. D., Chen, L. L., & Tai, P. C. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.16.6164 · Cited by 294
Altered NADH/NAD + Ratio Mediates Coresistance to Isoniazid and Ethionamide in Mycobacteria
Vilchèze, C., Weisbrod, T. R., Chen, B., Kremer, L., Hazbón, M. H., Wang, F., Alland, D., Sacchettini, J. C., & Jacobs, W. R. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.2.708-720.2005 · Cited by 284
Tuberculosis and the Tubercle Bacillus
Cole, S. T. (2004) · Wiley eBooks · doi:10.1128/9781555817657 · Cited by 270
ALTERNATIVECANDIDA ALBICANSLIFESTYLES: Growth on Surfaces
Kumamoto, C. A., & Vinces, M. D. (2005) · Annual Review of Microbiology · doi:10.1146/annurev.micro.59.030804.121034 · Cited by 247
Vázquez‐Laslop, N., Lee, H., & Neyfakh, A. A. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.10.3494-3497.2006 · Cited by 231
Programmed Cell Death in Escherichia coli : Some Antibiotics Can Trigger mazEF Lethality
Sat, B., Hazan, R., Fisher, T., Khaner, H., Glaser, G., & Engelberg–Kulka, H. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.6.2041-2045.2001 · Cited by 228
Mack, D., Becker, P., Chatterjee, I., Dobinsky, S., Knobloch, J. K. ‐., Peters, G., Rohde, H., & Herrmann, M. (2004) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2004.06.015 · Cited by 226
Korch, S. B., & Hill, T. (2006) · Journal of Bacteriology · doi:10.1128/jb.01740-05 · Cited by 225
GlpD and PlsB Participate in Persister Cell Formation in Escherichia coli
Spoering, A. L., Vulić, M., & Lewis, K. (2006) · Journal of Bacteriology · doi:10.1128/jb.00369-06 · Cited by 214
Self-citationHarrison, J. J., Turner, R. J., & Ceri, H. (2005) · Environmental Microbiology · doi:10.1111/j.1462-2920.2005.00777.x · Cited by 213
Phenotypic Tolerance: Antibiotic Enrichment of Noninherited Resistance in Bacterial Populations
Wiuff, C., Zappala, R. M., Regoes, R. R., Garner, K. N., Baquero, F., & Levin, B. R. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.4.1483-1494.2005 · Cited by 213
CORREIA, F. F., Donofrio, A. E., Rejtar, T., Li, L., Karger, B. L., Makarova, K. S., Koonin, E. V., & Lewis, K. (2006) · Journal of Bacteriology · doi:10.1128/jb.01237-06 · Cited by 199
Self-citationVetting, M. W., Hegde, S. S., Fajardo, J. E., Fiser, A., Roderick, S. L., Takiff, H. E., & Blanchard, J. S. (2005) · Biochemistry · doi:10.1021/bi052130w · Cited by 186
Moyed, H. S., & Broderick, S. H. (1986) · Journal of Bacteriology · doi:10.1128/jb.166.2.399-403.1986 · Cited by 176
McCool, J. D., Long, E., Petrosino, J. F., Sandler, H. A., Rosenberg, S. M., & Sandler, S. J. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04225.x · Cited by 169
Biofilms, Infection, and Antimicrobial Therapy
(2005) · CRC Press eBooks · doi:10.1201/9781420028232 · Cited by 168
Black, D. S., Kelly, A. J., Mardis, M. J., & Moyed, H. S. (1991) · Journal of Bacteriology · doi:10.1128/jb.173.18.5732-5739.1991 · Cited by 161
Black, D. S., Irwin, B., & Moyed, H. S. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.13.4081-4091.1994 · Cited by 150
Chung, J. D., Stephanopoulos, G. N., Ireton, K., & Grossman, A. D. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.7.1977-1984.1994 · Cited by 148
In search of natural substrates and inhibitors of MDR pumps.
Lewis, K. (2001) · PubMed · Cited by 127
Self-citationFalla, T. J., & Chopra, I. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.12.3282 · Cited by 119
The bactericidal action of penicillin: new clues to an unsolved mystery
Bayles, K. W. (2000) · Trends in Microbiology · doi:10.1016/s0966-842x(00)01762-5 · Cited by 116
Persister cells mediate tolerance to metal oxyanions in Escherichia coli
Harrison, J. J., Ceri, H., Roper, N. J., Badry, E. A., Sproule-Willoughby, K. M., & Turner, R. J. (2005) · Microbiology · doi:10.1099/mic.0.27794-0 · Cited by 114
A Novel Family of Escherichia coli Toxin-Antitoxin Gene Pairs
Brown, J., & Shaw, K. J. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.22.6600-6608.2003 · Cited by 110
Scherrer, R., & Moyed, H. S. (1988) · Journal of Bacteriology · doi:10.1128/jb.170.8.3321-3326.1988 · Cited by 103
The Ribosome Modulation Factor (RMF) Binding Site on the 100S Ribosome of Escherichia coli
Yoshida, H., Maki, Y., Kato, H., Fujisawa, H., Izutsu, K., Wada, C., & Wada, A. (2002) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a003313 · Cited by 91
Bacterial Resistance to Antimicrobials
(2002) · Journal of Tropical Pediatrics · doi:10.1093/tropej/48.5.318 · Cited by 84
Hu, Y., & Coates, A. R. M. (2004) · FEMS Microbiology Letters · doi:10.1016/j.femsle.2004.11.049 · Cited by 71
Heath, R. J., & Rock, C. O. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.6.1944-1946.1999 · Cited by 33
Flagged first, then by citations
1 of the 77 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- Hooper, D. C. in Bacterial Resistance to Antimicrobials: Mechanisms, Genetics, Medical Practice and Public Health (eds Lewis, K., Salyers A., Taber H. & Wax, R.) 161–192 (Marcell Dekker, New York, 2002).
- Walker, G. C. in Cell. Mol. Biol. (ed. Neidhardt, F. C.) 1400–1416 (ASM Press, Washington DC, 1996).
- Morgan, H. C., Meier, J. F. & Merker, R. L. Method of creating a biostatic agent using interpenetrating network polymers. US Patent 6, 146, 688 (2000).
- Hurst, C. J. Divining the future of microbiology. ASM News 71, 262–263 (2005).
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Metadata
- Authors
- Lewis, K.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Lewis, Kim
- ORCID
- Lewis, Kim
- Venue
- Nature Reviews Microbiology
- Published
- 2006-12-04
- Volume
- 5
- Issue
- 1
- Pages
- 48-56
- ISSN
- 1740-1526 (ISSN-L)
- 1740-1534
- OpenAlex
- W2045825103
- Cited by
- 2,052
- References
- 77
- Citations by year
- 2026: 101 · 2025: 98 · 2024: 104 · 2023: 116 · 2022: 126 · 2021: 129 · 2020: 127 · 2019: 132 · 2018: 122 · 2017: 100 · 2016: 120 · 2015: 130 · 2014: 94 · 2013: 104 · 2012: 108
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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, bacterial dormancy, antibiotic tolerance, persistent infection, unculturable microorganisms, multidrug tolerance
- MeSH terms
- Adaptation, Physiological, Anti-Bacterial Agents, Bacteria, Bacterial Infections, Drug Tolerance, Genes, Bacterial, Humans, Gene Expression Regulation, Bacterial, Bacterial Physiological Phenomena, Biofilms, Drug Resistance, Multiple, Bacterial, Microbial Viability
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