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 cellular metabolism temporarily ceases.
“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]
Antifungal resistance is linked to specific molecular mechanisms and can be stably inherited by progeny.
“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]
Antifungal persistence is non-heritable, although progeny of persisters may still divide into persistent and non-persistent subpopulations.
“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]
Dormant state reduces exposure of antibiotic targets and helps bacterial cells tolerate a variety of antibiotics, a process linked to the toxin-antitoxin system.
“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]
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 · see citing works
Antibacterial resistance worldwide: causes, challenges and responses
Levy, S. B., & Marshall, B. M. (2004) · Nature Medicine · doi:10.1038/nm1145 · Cited by 4,047 · see citing works
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 · see citing works
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 2,271 · see citing works
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 · see citing works
TOR, a central controller of cell growth.
Schmelzle, T., & Hall, M. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 2,044 · see citing works
Lewis, K. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.4.999-1007.2001 · Cited by 1,988 · see citing works
Self-citationQuorum-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 · see citing works
Staley, J. T., & Konopka, A. E. (1985) · Annual Review of Microbiology · doi:10.1146/annurev.mi.39.100185.001541 · Cited by 1,512 · see citing works
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 1,239 · see citing works
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 1,212 · see citing works
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 · see citing works
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 · see citing works
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 1,099 · see citing works
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 · see citing works
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 · see citing works
Spoering, A. L., & Lewis, K. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.23.6746-6751.2001 · Cited by 907 · see citing works
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 · see citing works
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 857 · see citing works
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 · see citing works
Connon, S. A., & Giovannoni, S. J. (2002) · Applied and Environmental Microbiology · doi:10.1128/aem.68.8.3878-3885.2002 · Cited by 742 · see citing works
Dubnau, D. A., & Losick, R. M. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05249.x · Cited by 729 · see citing works
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 · see citing works
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 646 · see citing works
Moyed, H. S., & Bertrand, K. P. (1983) · Journal of Bacteriology · doi:10.1128/jb.155.2.768-775.1983 · Cited by 632 · see citing works
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 · see citing works
Self-citationVuong, 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 623 · see citing works
Lewis, K. (2000) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.64.3.503-514.2000 · Cited by 614 · see citing works
Self-citationToxins-Antitoxins: Plasmid Maintenance, Programmed Cell Death, and Cell Cycle Arrest
Hayes, F. (2003) · Science · doi:10.1126/science.1088157 · Cited by 586 · see citing works
Cannibalism by sporulating bacteria.
González-Pastor, J. E., Hobbs, E. C., & Losick, R. (2003) · Science · doi:10.1126/science.1086462 · Cited by 579 · see citing works
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 568 · see citing works
Non-inherited antibiotic resistance
Levin, B. R., & Rozen, D. E. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1445 · Cited by 546 · see citing works
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 · see citing works
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 535 · see citing works
Microbial Cell Individuality and the Underlying Sources of Heterogeneity
Avery, S. V. (2006) · Nature Reviews Microbiology · doi:10.1038/nrmicro1460 · Cited by 521 · see citing works
<i>Candida albicans</i> 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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 368 · see citing works
Pedersen, K. B., Christensen, S. K., & Gerdes, K. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03027.x · Cited by 360 · see citing works
Christensen, S. K., & Gerdes, K. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03512.x · Cited by 338 · see citing works
Milović, N. M., Wang, J., Lewis, K., & Klibanov, A. M. (2005) · Biotechnology and Bioengineering · doi:10.1002/bit.20454 · Cited by 316 · see citing works
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 311 · see citing works
Self-citationLin, J., Qiu, S., Lewis, K., & Klibanov, A. M. (2003) · Biotechnology and Bioengineering · doi:10.1002/bit.10651 · Cited by 300 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Tuberculosis and the Tubercle Bacillus
Cole, S. T. (2004) · Wiley eBooks · doi:10.1128/9781555817657 · Cited by 270 · see citing works
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 236 · see citing works
Vázquez‐Laslop, N., Lee, H., & Neyfakh, A. A. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.10.3494-3497.2006 · Cited by 231 · see citing works
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 · see citing works
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 · see citing works
Korch, S. B., & Hill, T. (2006) · Journal of Bacteriology · doi:10.1128/jb.01740-05 · Cited by 225 · see citing works
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 215 · see citing works
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 · see citing works
Self-citationHarrison, J. J., Turner, R. J., & Ceri, H. (2005) · Environmental Microbiology · doi:10.1111/j.1462-2920.2005.00777.x · Cited by 213 · see citing works
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 · see citing works
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 · see citing works
Moyed, H. S., & Broderick, S. H. (1986) · Journal of Bacteriology · doi:10.1128/jb.166.2.399-403.1986 · Cited by 176 · see citing works
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 · see citing works
Biofilms, Infection, and Antimicrobial Therapy
(2005) · CRC Press eBooks · doi:10.1201/9781420028232 · Cited by 168 · see citing works
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 · see citing works
Black, D. S., Irwin, B., & Moyed, H. S. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.13.4081-4091.1994 · Cited by 150 · see citing works
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 · see citing works
In search of natural substrates and inhibitors of MDR pumps.
Lewis, K. (2001) · PubMed · Cited by 127 · see citing works
Self-citationFalla, T. J., & Chopra, I. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.12.3282 · Cited by 119 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Scherrer, R., & Moyed, H. S. (1988) · Journal of Bacteriology · doi:10.1128/jb.170.8.3321-3326.1988 · Cited by 103 · see citing works
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 · see citing works
Bacterial Resistance to Antimicrobials
(2002) · Journal of Tropical Pediatrics · doi:10.1093/tropej/48.5.318 · Cited by 84 · see citing works
Hu, Y., & Coates, A. R. M. (2004) · FEMS Microbiology Letters · doi:10.1016/j.femsle.2004.11.049 · Cited by 71 · see citing works
Heath, R. J., & Rock, C. O. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.6.1944-1946.1999 · Cited by 33 · see citing works
Flagged first, then by citations
1 of the 77 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
Sharma, S. V., Lee, D. Y., Li, B., Quinlan, M. P., Takahashi, F., Maheswaran, S., McDermott, U., Azizian, N., Zou, L., Fischbach, M. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.02.027 · Cited by 2,770 · see citing works
Physiological heterogeneity in biofilms
Stewart, P. S., & Franklin, M. J. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1838 · Cited by 2,480 · see citing works
Microbial seed banks: the ecological and evolutionary implications of dormancy
Lennon, J. T., & Jones, S. E. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2504 · Cited by 1,872 · see citing works
Lewis, K. (2010) · Annual Review of Microbiology · doi:10.1146/annurev.micro.112408.134306 · Cited by 1,858 · see citing works
Self-citationMolecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria
Hall, C. W., & Mah, T. (2017) · FEMS Microbiology Reviews · doi:10.1093/femsre/fux010 · Cited by 1,753 · see citing works
Fundamentals of Microbial Community Resistance and Resilience
Shade, A. L., Peter, H., Allison, S., Baho, D. L., Berga, M., Bürgmann, H., Huber, D. H., Langenheder, S., Lennon, J. T., Martiny, J. B. H., et al. (2012) · Frontiers in Microbiology · doi:10.3389/fmicb.2012.00417 · Cited by 1,728 · see citing works
Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review
Mulani, M. S., Kamble, E. E., Kumkar, S. N., Tawre, M. S., & Pardesi, K. R. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00539 · Cited by 1,663 · see citing works
Distinguishing between resistance, tolerance and persistence to antibiotic treatment
Brauner, A., Fridman, O., Gefen, O., & Balaban, N. Q. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.34 · Cited by 1,612 · see citing works
Pseudomonas aeruginosa Lifestyle: A Paradigm for Adaptation, Survival, and Persistence
Moradali, M. F., Ghods, S., & Rehm, B. H. A. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00039 · Cited by 1,554 · see citing works
Platforms for antibiotic discovery
Lewis, K. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3975 · Cited by 1,449 · see citing works
Self-citationLebeaux, D., Ghigo, J., & Beloin, C. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00013-14 · Cited by 1,321 · see citing works
Definitions and guidelines for research on antibiotic persistence
Balaban, N. Q., Helaine, S., Lewis, K., Ackermann, M., Aldridge, B., Andersson, D. I., Brynildsen, M. P., Bumann, D., Camilli, A., Collins, J. J., et al. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0196-3 · Cited by 1,313 · see citing works
Self-citationAntibiotic tolerance facilitates the evolution of resistance
Levin-Reisman, I., Ronin, I., Gefen, O., Braniss, I., Noam Shoresh, F., & Balaban, N. Q. (2017) · Science · doi:10.1126/science.aaj2191 · Cited by 1,229 · see citing works
The value of antimicrobial peptides in the age of resistance
Magana, M., Muthuirulan, P., Santos, A. L., Leanse, L. G., Fernández, M., Ioannidis, A., Giulianotti, M. A., Apidianakis, Y., Bradfute, S. B., Ferguson, A. L., et al. (2020) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30327-3 · Cited by 1,160 · see citing works
Helicobacter pylori treatment in the era of increasing antibiotic resistance
Graham, D. Y., & Fischbach, L. A. (2010) · Gut · doi:10.1136/gut.2009.192757 · Cited by 1,031 · see citing works
Metabolite-enabled eradication of bacterial persisters by aminoglycosides
Allison, K. R., Brynildsen, M. P., & Collins, J. J. (2011) · Nature · doi:10.1038/nature10069 · Cited by 1,025 · see citing works
Bistability, Epigenetics, and Bet-Hedging in Bacteria
Veening, J., Smits, W. K., & Kuipers, O. P. (2008) · Annual Review of Microbiology · doi:10.1146/annurev.micro.62.081307.163002 · Cited by 1,006 · see citing works
Bengtsson‐Palme, J., & Larsson, D. G. J. (2015) · Environment International · doi:10.1016/j.envint.2015.10.015 · Cited by 996 · see citing works
Quorum sensing inhibitors: An overview
Kalia, V. C. (2012) · Biotechnology Advances · doi:10.1016/j.biotechadv.2012.10.004 · Cited by 989 · see citing works
Efflux-Mediated Drug Resistance in Bacteria
Li, X.-Z., & Nikaido, H. (2009) · Drugs · doi:10.2165/11317030-000000000-00000 · Cited by 976 · see citing works
Active Starvation Responses Mediate Antibiotic Tolerance in Biofilms and Nutrient-Limited Bacteria
Nguyen, D. M., Joshi-Datar, A., Lepine, F. L., Bauerle, E., Olakanmi, O., Beer, K. D., McKay, G. A., Siehnel, R., Schafhauser, J., Wang, Y., et al. (2011) · Science · doi:10.1126/science.1211037 · Cited by 974 · see citing works
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Jones, S. E., & Lennon, J. T. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912765107 · Cited by 926 · see citing works
Hurdle, J. G., O’Neill, A. J., Chopra, I., & Lee, R. E., Jr. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2474 · Cited by 871 · see citing works
Antibiotic resistance and persistence—implications for human health and treatment perspectives
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The Science of Antibiotic Discovery
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Uruén, C., Chopo‐Escuin, G., Tommassen, J., Jaime, R. C. M., & Arenas, J. (2020) · Antibiotics · doi:10.3390/antibiotics10010003 · Cited by 812 · see citing works
Microbial biofilm: formation, architecture, antibiotic resistance, and control strategies
Rather, M. A., Gupta, K., & Mandal, M. (2021) · Brazilian Journal of Microbiology · doi:10.1007/s42770-021-00624-x · Cited by 810 · see citing works
Ciprofloxacin Causes Persister Formation by Inducing the TisB toxin in Escherichia coli
Dörr, T., Vulić, M., & Lewis, K. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000317 · Cited by 781 · see citing works
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Rabin, N., Zheng, Y., Opoku‐Temeng, C., Du, Y., Bonsu, E., & Sintim, H. O. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.6 · Cited by 751 · see citing works
Variable Clonal Repopulation Dynamics Influence Chemotherapy Response in Colorectal Cancer
Kreso, A., O'Brien, C. A., van Galen, P., Gan, O. I., Notta, F., Brown, A. M. K., Ng, K., Ma, J., Wienholds, E., Dunant, C. F., et al. (2012) · Science · doi:10.1126/science.1227670 · Cited by 738 · see citing works
Strategies for culture of ‘unculturable’ bacteria
Vartoukian, S. R., Palmer, R. M. J., & Wade, W. G. (2010) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2010.02000.x · Cited by 721 · see citing works
Bacterial Persister Cell Formation and Dormancy
Wood, T. K., Knabel, S. J., & Kwan, B. W. (2013) · Applied and Environmental Microbiology · doi:10.1128/aem.02636-13 · Cited by 705 · see citing works
Assembly and Development of the Pseudomonas aeruginosa Biofilm Matrix
Luyan, Z., Conover, M., Lu, H., Parsek, M. R., Bayles, K. W., & Wozniak, D. J. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000354 · Cited by 703 · see citing works
Understanding the Mechanism of Bacterial Biofilms Resistance to Antimicrobial Agents
Singh, S., Singh, S. K., Chowdhury, I., & Singh, R. (2017) · The Open Microbiology Journal · doi:10.2174/1874285801711010053 · Cited by 696 · see citing works
Candida Biofilms: Threats, Challenges, and Promising Strategies
Cavalheiro, M., & Teixeira, M. C. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00028 · Cited by 690 · see citing works
Biofilm formation and the food industry, a focus on the bacterial outer surface
Houdt, R. V., & Michiels, C. W. (2010) · Journal of Applied Microbiology · doi:10.1111/j.1365-2672.2010.04756.x · Cited by 688 · see citing works
West, S. A., Diggle, S. P., Buckling, A. G. J., Gardner, A., & Griffin, A. S. (2007) · Annual Review of Ecology Evolution and Systematics · doi:10.1146/annurev.ecolsys.38.091206.095740 · Cited by 679 · see citing works
Multimetal resistance and tolerance in microbial biofilms
Harrison, J. J., Ceri, H., & Turner, R. J. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1774 · Cited by 666 · see citing works
Nadell, C. D., Xavier, J. B., & Foster, K. R. (2008) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2008.00150.x · Cited by 654 · see citing works
Development and regulation of single- and multi-species Candida albicans biofilms
Lohse, M. B., Gulati, M., Johnson, A. D., & Nobile, C. J. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.107 · Cited by 643 · see citing works
Losick, R. M., & Desplan, C. (2008) · Science · doi:10.1126/science.1147888 · Cited by 627 · see citing works
Mulcahy, L. R., Burns, J. L., Lory, S. J., & Lewis, K. (2010) · Journal of Bacteriology · doi:10.1128/jb.01651-09 · Cited by 621 · see citing works
Self-citationInnovations to culturing the uncultured microbial majority
Lewis, W. H., Tahon, G., Geesink, P., Sousa, D. Z., & Ettema, T. J. G. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-020-00458-8 · Cited by 614 · see citing works
Importance of prophages to evolution and virulence of bacterial pathogens
Fortier, L., & Sekulović, O. (2013) · Virulence · doi:10.4161/viru.24498 · Cited by 583 · see citing works
Microbial Population and Community Dynamics on Plant Roots and Their Feedbacks on Plant Communities
Bever, J. D., Platt, T. G., & Morton, E. R. (2012) · Annual Review of Microbiology · doi:10.1146/annurev-micro-092611-150107 · Cited by 574 · see citing works
Salmonella biofilms: An overview on occurrence, structure, regulation and eradication
Steenackers, H. P. L., Hermans, K., Vanderleyden, J., & Keersmaecker, S. C. J. D. (2011) · Food Research International · doi:10.1016/j.foodres.2011.01.038 · Cited by 567 · see citing works
From in vitro to in vivo Models of Bacterial Biofilm-Related Infections
Lebeaux, D., Chauhan, A., Rendueles, O., & Beloin, C. (2013) · Pathogens · doi:10.3390/pathogens2020288 · Cited by 551 · see citing works
Ojha, A. K., Baughn, A. D., Sambandan, D., Hsu, T., Trivelli, X., Guérardel, Y., Alahari, A., Kremer, L., Jacobs, W. R., & Hatfull, G. F. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06274.x · Cited by 541 · see citing works
Cationic Antimicrobial Polymers and Their Assemblies
Carmona‐Ribeiro, A. M., & Carrasco, L. D. D. M. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14059906 · Cited by 531 · see citing works
SOS Response Induces Persistence to Fluoroquinolones in Escherichia coli
Dörr, T., Lewis, K., & Vulić, M. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000760 · Cited by 530 · see citing works
Self-citationEngineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy
Lu, T. K., & Collins, J. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800442106 · Cited by 522 · see citing works
Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm
Soto, S. M. (2013) · Virulence · doi:10.4161/viru.23724 · Cited by 521 · see citing works
Pseudomonas aeruginosa Biofilms in Disease
Mulcahy, L. R., Isabella, V. M., & Lewis, K. (2013) · Microbial Ecology · doi:10.1007/s00248-013-0297-x · Cited by 517 · see citing works
Self-citationGan, B., Gaynord, J. S., Rowe, S. M., Deingruber, T., & Spring, D. R. (2021) · Chemical Society Reviews · doi:10.1039/d0cs00729c · Cited by 516 · see citing works
Huddleston, J. R. (2014) · Infection and Drug Resistance · doi:10.2147/idr.s48820 · Cited by 515 · see citing works
Role of bacterial efflux pumps in biofilm formation
Alav, I., Sutton, J. M., & Rahman, K. M. (2018) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dky042 · Cited by 504 · see citing works
Terpene Derivatives as a Potential Agent against Antimicrobial Resistance (AMR) Pathogens
Mahizan, N. A., Yang, S.-K., Moo, C.-L., Song, A. A., Chong, C. M., Chong, C. W., Abushelaibi, A. A., Lim, S. E., & Lai, K. (2019) · Molecules · doi:10.3390/molecules24142631 · Cited by 491 · see citing works
Pathogenesis ofCandida albicansbiofilm
Tsui, C., Kong, E. F., & Jabra‐Rizk, M. A. (2016) · Pathogens and Disease · doi:10.1093/femspd/ftw018 · Cited by 487 · see citing works
Prevention and control of biofilm-based medical-device-related infections
Francolini, I., & Donelli, G. (2010) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2010.00665.x · Cited by 473 · see citing works
Siderophores from Neighboring Organisms Promote the Growth of Uncultured Bacteria
Donofrio, A. E., Crawford, J. M., Stewart, E. J., Witt, K., Gavrish, E., Epstein, S. S., Clardy, J., & Lewis, K. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.02.010 · Cited by 457 · see citing works
Self-citationAsymmetry and Aging of Mycobacterial Cells Lead to Variable Growth and Antibiotic Susceptibility
Aldridge, B. B., Fernandez-Suarez, M., Heller, D., Ambravaneswaran, V., Irimia, D., Toner, M., & Fortune, S. M. (2012) · Science · doi:10.1126/science.1216166 · Cited by 454 · see citing works
A review of the recent advances in antimicrobial coatings for urinary catheters
Singha, P., Locklin, J., & Handa, H. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.11.070 · Cited by 454 · see citing works
Simões, M. V., Bennett, R. N., & Rosa, E. A. S. (2009) · Natural Product Reports · doi:10.1039/b821648g · Cited by 451 · see citing works
Antimicrobial Tolerance in Biofilms
Stewart, P. S. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mb-0010-2014 · Cited by 450 · see citing works
Bacterial and Fungal Biofilm Infections
Lynch, A. S., & Robertson, G. T. (2007) · Annual Review of Medicine · doi:10.1146/annurev.med.59.110106.132000 · Cited by 448 · see citing works
Microbial Contamination of Drinking Water and Human Health from Community Water Systems
Ashbolt, N. J. (2015) · Current Environmental Health Reports · doi:10.1007/s40572-014-0037-5 · Cited by 442 · see citing works
Oncogene addiction: setting the stage for molecularly targeted cancer therapyPreprint
Sharma, S. V., & Settleman, J. E. (2007) · Genes & Development · doi:10.1101/gad.1609907 · Cited by 442 · see citing works
Maisonneuve, E., Castro-Camargo, M., & Gerdes, K. (2013) · Cell · doi:10.1016/j.cell.2013.07.048 · Cited by 439 · see citing works
RetractedTuchscherr, L., Medina, E., Hussain, M., Völker, W., Heitmann, V., Niemann, S., Holzinger, D., Roth, J., Proctor, R. A., Becker, K., et al. (2011) · EMBO Molecular Medicine · doi:10.1002/emmm.201000115 · Cited by 437 · see citing works
Wang, X., & Wood, T. K. (2011) · Applied and Environmental Microbiology · doi:10.1128/aem.05068-11 · Cited by 431 · see citing works
Environmental factors that shape biofilm formation
Toyofuku, M., Inaba, T., Kiyokawa, T., Obana, N., Yawata, Y., & Nomura, N. (2016) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2015.1058701 · Cited by 429 · see citing works
Fauvart, M., De Groote, V. N., & Michiels, J. (2011) · Journal of Medical Microbiology · doi:10.1099/jmm.0.030932-0 · Cited by 425 · see citing works
Challenges of intervention, treatment, and antibiotic resistance of biofilm-forming microorganisms
Gebreyohannes, G., Nyerere, A. K., Bii, C. C., & Sbhatu, D. B. (2019) · Heliyon · doi:10.1016/j.heliyon.2019.e02192 · Cited by 419 · see citing works
Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis
Scorzoni, L., de Paula e Silva, A. C. A., Marcos, C. M., Assato, P. A., de Melo, W. C. M. A., de Oliveira, H. C., Costa-Orlandi, C. B., Mendes-Giannini, M. J. S., & Fusco-Almeida, A. M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00036 · Cited by 418 · see citing works
Signaling-mediated bacterial persister formation
Vega, N. M., Allison, K. R., Khalil, A. S., & Collins, J. J. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.915 · Cited by 415 · see citing works
Evolutionary Determinants of Cancer
Greaves, M. F. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0439 · Cited by 411 · see citing works
Present status and future directions – irrigants and irrigation methods
Boutsioukis, C., & Arias‐Moliz, M. T. (2022) · International Endodontic Journal · doi:10.1111/iej.13739 · Cited by 410 · see citing works
Bacterial Growth and Cell Division: a Mycobacterial Perspective
Hett, E. C., & Rubin, E. J. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00028-07 · Cited by 408 · see citing works
The Systemic Imprint of Growth and Its Uses in Ecological (Meta)Genomics
Vieira‐Silva, S., & Rocha, E. P. C. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000808 · Cited by 408 · see citing works
Effect of DNase and Antibiotics on Biofilm Characteristics
Tetz, G. V., Artemenko, N. K., & Tetz, V. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00471-08 · Cited by 402 · see citing works
Mechanisms of survival, responses and sources of Salmonella in low-moisture environments
Finn, S., Condell, O., Mcclure, P. J., Amézquita, A., & Fanning, S. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00331 · Cited by 401 · see citing works
Antimicrobial peptides and their interaction with biofilms of medically relevant bacteria
Batoni, G., Maisetta, G., & Esin, S. (2015) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2015.10.013 · Cited by 400 · see citing works
Pu, Y., Li, Y., Jin, X., Tian, T., Ma, Q., Zhao, Z., Lin, S.-Y., Chen, Z., Li, B., Yao, G., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.10.022 · Cited by 387 · see citing works
Formation, physiology, ecology, evolution and clinical importance of bacterial persisters
den Bergh, B. V., Fauvart, M., & Michiels, J. J. (2017) · FEMS Microbiology Reviews · doi:10.1093/femsre/fux001 · Cited by 380 · see citing works
Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells
Pu, Y., Zhao, Z., Li, Y., Zou, J., Ma, Q., Zhao, Y., Ke, Y., Zhu, Y., Chen, H., Baker, M. A. B., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.03.035 · Cited by 379 · see citing works
Lessons learned and unlearned in periodontal microbiology
Teles, R. P., Teles, F., Frias‐Lopez, J., Paster, B. J., & Haffajee, A. D. (2013) · Periodontology 2000 · doi:10.1111/prd.12010 · Cited by 377 · see citing works
Pseudomonas aeruginosa Biofilms: Host Response and Clinical Implications in Lung Infections
Maurice, N. M., Bedi, B., & Sadikot, R. T. (2018) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2017-0321tr · Cited by 375 · see citing works
Functional Roles of Pulsing in Genetic Circuits
Levine, J. H., Lin, Y., & Elowitz, M. B. (2013) · Science · doi:10.1126/science.1239999 · Cited by 369 · see citing works
Ramanathan, S., Santhakumari, S., Poonguzhali, P., Mani, G., Dyavaiah, M., & Xiangmin, L. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.676458 · Cited by 363 · see citing works
Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response
Grant, S. S., & Hung, D. T. (2013) · Virulence · doi:10.4161/viru.23987 · Cited by 362 · see citing works
Bertrand, R. L. (2019) · Journal of Bacteriology · doi:10.1128/jb.00697-18 · Cited by 361 · see citing works
A Model of Bacterial Intestinal Infections in Drosophila melanogaster
Nehme, N. T., Liégeois, S., Kele, B., Giammarinaro, P., Pradel, E., Hoffmann, J. A., Ewbank, J. J., & Ferrandon, D. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030173 · Cited by 358 · see citing works
Arrested Protein Synthesis Increases Persister-Like Cell Formation
Kwan, B. W., Valenta, J. A., Benedik, M. J., & Wood, T. K. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02135-12 · Cited by 358 · see citing works
New concepts of resistance in the treatment of Helicobacter pylori infections
Graham, D. Y., & Shiotani, A. (2008) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep1138 · Cited by 357 · see citing works
Moal, V. L.-L., & Servin, A. L. (2014) · Clinical Microbiology Reviews · doi:10.1128/cmr.00080-13 · Cited by 355 · see citing works
Molecular Mechanisms of HipA-Mediated Multidrug Tolerance and Its Neutralization by HipB
Schumacher, M. A., Piro, K. M., Xu, W., Hansen, S., Lewis, K., & Brennan, R. G. (2009) · Science · doi:10.1126/science.1163806 · Cited by 351 · see citing works
Self-citationRegulation of phenotypic variability by a threshold-based mechanism underlies bacterial persistence
Rotem, E., Loinger, A., Ronin, I., Levin-Reisman, I., Gabay, C., Noam Shoresh, F., Biham, O., & Balaban, N. Q. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004333107 · Cited by 351 · see citing works
Packiavathy, I. A. S. V., Agilandeswari, P., Musthafa, K. S., Pandian, S. K., & Ravi, A. V. (2011) · Food Research International · doi:10.1016/j.foodres.2011.10.022 · Cited by 348 · see citing works
Kuroda, K., Caputo, G. A., & DeGrado, W. F. (2008) · Chemistry - A European Journal · doi:10.1002/chem.200801523 · Cited by 346 · see citing works
Bacteriophage therapy against Pseudomonas aeruginosa biofilms: a review
Chegini, Z., Khoshbayan, A., Moghadam, M. T., Farahani, I. K., Jazireian, P., & Shariati, A. (2020) · Annals of Clinical Microbiology and Antimicrobials · doi:10.1186/s12941-020-00389-5 · Cited by 342 · see citing works
- 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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