Cited by 691Antibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyPharmaceutical and Antibiotic Environmental Impacts

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Tetracycline resistance determinants: mechanisms of action, regulation of expression, genetic mobility, and distribution

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Roberts, Marily C.·1996·FEMS Microbiology Reviews

DOI 10.1111/j.1574-6976.1996.tb00251.x

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Abstract

Tetracycline-resistant bacteria were first isolated in 1953 from Shigella dysenteriae, a bacterium which causes bacterial dysentery. Since then tetracycline-resistant bacterial have been found in increasing numbers of species and genera. This has resulted in reduced effectiveness of tetracycline therapy over time. Tetracycline resistance is normally due to the acquisition of new genes often associated with either a mobile plasmid or a transposon. These tetracycline resistance determinants are distinguishable both genetically and biochemically. Resistance is primarily due to either energy-dependent efflux of tetracycline or protection of the ribosomes from the action of tetracycline. Gram-negative tetracycline efflux proteins are linked to repressor proteins which in the absence of tetracycline block transcription of the repressor and structural efflux genes. In contrast, expression of the Gram-positive tetracycline efflux genes and some of the ribosomal protection genes appears to be regulated by attenuation of mRNA transcription. Specific tetracycline resistance genes have been identified in 32 Gram-negative and 22 Gram-positive genera. Tetracycline-resistant bacteria are found in pathogens, opportunistic and normal flora species. Tetracycline-resistant bacteria can be isolated from man, animals, food, and the environment. The nonpathogens in each of these ecosystems may play an important role as reservoirs for the antibiotic resistance genes. It is clear that if we are to reverse the trend toward increasingly antibiotic-resistant pathogenic bacteria we will need to change how antibiotics are used in both human and animal health and food production.

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Roberts, M. C., McFarland, L. V., Mullany, P. P., & Mulligan, M. E. (1994) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/33.3.419 · Cited by 40
Self-citation
Tet determinants provide poor protection against some tetracyclines: further evidence for division of tetracyclines into two classes
Oliva, B., & Chopra, I. (1992) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.36.4.876 · Cited by 40
Cloning, Expression in Escherichia coli and Nucleotide Sequence of a Tetracycline-resistance Gene from Streptomyces rimosus
REYNES, J. P., Calmels, T., Drocourt, D., & Tiraby, G. (1988) · Microbiology · doi:10.1099/00221287-134-3-585 · Cited by 40
Tet protein domains interact productively to mediate tetracycline resistance when present on separate polypeptides
Rubin, R. A., & Levy, S. B. (1991) · Journal of Bacteriology · doi:10.1128/jb.173.14.4503-4509.1991 · Cited by 38
Characterization of antibiotic-resistant Corynebacterium striatum strains
Roberts, M. C., Leonard, R. B., Briselden, A. M., Schoenknecht, F. D., & Coyle, M. B. (1992) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/30.4.463 · Cited by 37
Self-citation
tRNA modification activity is necessary for Tet(M)-mediated tetracycline resistance
Burdett, V. (1993) · Journal of Bacteriology · doi:10.1128/jb.175.22.7209-7215.1993 · Cited by 36
Origin of tetracycline efflux proteins: conclusions from nucleotide sequence analysis
Sheridan, R. P., & Chopra, I. (1991) · Molecular Microbiology · doi:10.1111/j.1365-2958.1991.tb00763.x · Cited by 36
Detection of two groups of 25·2 MDa Tet M plasmids by polymerase chain reaction of the downstream region
Xia, M., Pang, Y., & Roberts, M. C. (1995) · Molecular and Cellular Probes · doi:10.1016/s0890-8508(95)91620-2 · Cited by 35
Self-citation
Molecular characterization of "plasmid-free" antibiotic-resistant Haemophilus influenzae
Roberts, M. C., & Smith, A. L. (1980) · Journal of Bacteriology · doi:10.1128/jb.144.1.476-479.1980 · Cited by 34
Self-citation
Genetic basis of antibiotic resistance in Aerococcus viridans
Buu-Hoï, A., Bouguénec, C. L., & Horaud, T. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.4.529 · Cited by 34
A DNA sequence upstream of the tet(O) gene is required for full expression of tetracycline resistance
Wang, Y., & Taylor, D. E. (1991) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.35.10.2020 · Cited by 34
A new tetracycline antibiotic with antitumor activity. II. The structural elucidation of SF2575.
Hatsu, M., Sasaki, T., Gomi, S., Kodama, Y., Sezaki, M., Inouye, S., & Kondo, S. (1992) · The Journal of Antibiotics · doi:10.7164/antibiotics.45.325 · Cited by 33
Introduction of transposon Tn916 DNA into Haemophilus influenzae and Haemophilus parainfluenzae
Kauc, L., & Goodgal, S. H. (1989) · Journal of Bacteriology · doi:10.1128/jb.171.12.6625-6628.1989 · Cited by 32
N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6-desoxytetracycline, two new glycylcyclines highly effective against tetracycline-resistant gram-positive cocci
Goldstein, F. W., Kitzis, M.-D., & Acar, J. F. (1994) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.38.9.2218 · Cited by 30
Tetracycline resistance determinants, Tet B and Tet M, detected in Pasteurella haemolytica and Pasteurella multocida from bovine herds
Chaslus-Dancla, E., Lesage-Descauses, M.-C., Léroy, S., Martel, J. L., & Lafont, J.-P. (1995) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/36.5.815 · Cited by 30
Plasmid-mediated Tet M in Haemophilus ducreyi
Roberts, M. C. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.9.1611 · Cited by 30
Self-citation
Cloning and characterization of tetM gene from a Ureaplasma urealyticum strain
Brown, J. T., & Roberts, M. C. (1987) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.31.11.1852 · Cited by 28
Self-citation
Tetracycline resistance determinants in streptococcal species isolated from the bovine mammary gland
Brown, M. B., & Roberts, M. C. (1991) · Veterinary Microbiology · doi:10.1016/0378-1135(91)90124-x · Cited by 28
Self-citation
Dactylocyclines: novel tetracycline glycosides active against tetracycline-resistant bacteria
Tymiak, A. A., AKLONIS, C. A., Bolgar, M. S., KAHLE, A. D., Kirsch, D. R., O''SULLIVAN, J., Porubcan, M. A., Principe, P. A., & TREJO, W. H. (1993) · The Journal of Organic Chemistry · doi:10.1021/jo00055a002 · Cited by 28
The tet(Q) gene in bacteria isolated from patients with refractory periodontal disease
Olsvik, B., Olsen, I., & Tenover, F. C. (1994) · Oral Microbiology and Immunology · doi:10.1111/j.1399-302x.1994.tb00067.x · Cited by 27
Molecular cloning of a tetracycline-resistance determinant from Bacillus subtilis chromosomal DNA and its expression in Escherichia coli and B. subtilis
Sakaguchi, R., & Shishido, K. (1988) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(88)90053-x · Cited by 26
Tetracycline resistance in Moraxella (Branhamella) catarrhalis: demonstration of two clonal outbreaks by using pulsed-field gel electrophoresis
Roberts, M. C., Pang, Y. J., Spencer, R. C., Winstanley, T. G., Brown, B. A., & Wallace, R. J. (1991) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.35.11.2453 · Cited by 25
Self-citation
Mutational and physiological analyses of plasmid pT181 functions expressing incompatibility
Highlander, S. K., & Novick, R. P. (1990) · Plasmid · doi:10.1016/0147-619x(90)90039-f · Cited by 24
The unstable tetracycline resistance gene of Streptomyces lividans 1326 encodes a putative protein with similarities to translational elongation factors and Tet(M) and Tet(O) proteins
Dittrich, W., & Schrempf, H. (1992) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.36.5.1119 · Cited by 22
Oligonucleotide probe determination of tetracycline-resistant bacteria isolated from catfish ponds
DePaola, A., Hill, W. E., & Harrell, F. (1993) · Molecular and Cellular Probes · doi:10.1006/mcpr.1993.1051 · Cited by 20
Genetic analysis suggests functional interactions between the N- and C-terminal domains of the TetA(C) efflux pump encoded by pBR322
McNicholas, P. M., McGlynn, M., Guay, G. G., & Rothstein, D. M. (1995) · Journal of Bacteriology · doi:10.1128/jb.177.18.5355-5357.1995 · Cited by 20
Transposon Tn10-like tetracycline resistance determinants in Haemophilus parainfluenzae
Levy, S. B., Buu-Hoï, A., & Marshall, B. M. (1984) · Journal of Bacteriology · doi:10.1128/jb.160.1.87-94.1984 · Cited by 19
Characterization of unusual tetracycline-resistant gram-positive bacteria
Roberts, M. C., Moncla, B. J., & Hillier, S. L. (1991) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.35.12.2655 · Cited by 19
Self-citation
Minocycline: old and new therapeutic uses
Freeman, C. D., Nightingale, C. H., & Quintiliani, R. (1994) · International Journal of Antimicrobial Agents · doi:10.1016/0924-8579(94)90034-5 · Cited by 18
Susceptibility of Bacteroides ureolyticus to antimicrobial agents and identification of a tetracycline resistance determinant related to tetM
de Barbeyrac, B., Dutilh, B., Quentin, C., Renaudin, H., & Bébéar, C. (1991) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/27.6.721 · Cited by 18
Frequency of four classes of tetracycline resistance determinants in Salmonella and Shigella spp. clinical isolates
Martı́nez-Salazar, J. M., Alvarez, G., & Gómez‐Eichelmann, M. C. (1986) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.30.4.630 · Cited by 17
Constitutive expression of tetracycline resistance mediated by a Tn10-like element in Haemophilus parainfluenzae results from a mutation in the repressor gene
Heuer, C., Hickman, R. K., Curiale, M. S., Hillen, W., & Levy, S. B. (1987) · Journal of Bacteriology · doi:10.1128/jb.169.3.990-994.1987 · Cited by 15
Evolutionary Aspects of Plasmid Mediated Resistance in a Hospital Environment
Acar, J. F., Bouanchaud, D. H., & CHABBERT, Y. A. (1977) · Topics in infectious diseases · doi:10.1007/978-3-7091-8501-8_1 · Cited by 11
Tetracycline resistance genes in Kenyan hospital isolates of Salmonella typhimurium
Kariuki, S., Nb, M., Wasteson, Y., Senerwa, D., Gathuma, J. M., & Olsvik, Ø. (1992) · Apmis · doi:10.1111/j.1699-0463.1992.tb03977.x · Cited by 10
Cloning of a probe for a previously undescribed enterobacterial tetracycline resistance gene
Jones, C. S., Osborne, D. J., & Stanley, J. (1992) · Letters in Applied Microbiology · doi:10.1111/j.1472-765x.1992.tb00738.x · Cited by 9
A truncated Tn916-like element in a clinical isolate of Enterococcus faecium
Fletcher, H. M., & Daneo-Moore, L. (1992) · Plasmid · doi:10.1016/0147-619x(92)90015-3 · Cited by 8
Transfer Frequency of Various 25.2 Mdal Tetracycline Resistance Plasmids in Neisseria gonorrhoeae
Roberts, M. C., & Knapp, J. S. (1989) · Sexually Transmitted Diseases · doi:10.1097/00007435-198904000-00010 · Cited by 5
Self-citation

Research works printed but not linked: 2

10.1093/jac/33.3.419 · DOI
Nelson W.L. Kuritsky J.N. Kennedy D.L. Lao C.S. (1987) Outpatient (outpt) pediatric antibiotic use in the US: trends and therapy for otitis media (OM) 1977–1986, In: Program and Abstracts of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy pp 175 American Society for Microbiology, Washington, DC Abstract 455.

Sorted by citations

Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance
Chopra, I., & Roberts, M. (2001) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.65.2.232-260.2001 · Cited by 4,517
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Antibacterial resistance worldwide: causes, challenges and responses
Levy, S. B., & Marshall, B. M. (2004) · Nature Medicine · doi:10.1038/nm1145 · Cited by 4,152
Recombinant protein expression in Escherichia coli: advances and challenges
Rosano, G. L., & Ceccarelli, E. A. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00172 · Cited by 2,556
Resistance to Antibiotics: Are We in the Post-Antibiotic Era?
Alanis, A. J. (2005) · Archives of Medical Research · doi:10.1016/j.arcmed.2005.06.009 · Cited by 1,458
The threat of antimicrobial resistance in developing countries: causes and control strategies
Ayukekbong, J. A., Ntemgwa, M., & Atabe, A. N. (2017) · Antimicrobial Resistance & Infection Control · doi:10.1186/s13756-017-0208-x · Cited by 1,315

See all 691

Authors: Roberts, M. C.
Venue: FEMS Microbiology Reviews
Publisher: Oxford University Press (OUP)
Published: 1996-10
Volume: 19
Issue: 1
Pages: 1-24
ISSN: 0168-6445 (ISSN-L)
1574-6976
DOI: 10.1111/j.1574-6976.1996.tb00251.x
OpenAlex: W2165499943
Cited by: 689
References: 130
Citations by year: 2026: 20 · 2025: 18 · 2024: 22 · 2023: 21 · 2022: 33 · 2021: 48 · 2020: 29 · 2019: 26 · 2018: 34 · 2017: 21 · 2016: 25 · 2015: 15 · 2014: 20 · 2013: 34 · 2012: 18
FWCI: 6.51
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: FEMS Microbiology Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Agriculture
National Institutes of Health (5r01ai024136-08, 5r03de010913-02)
National Institute of Allergy and Infectious Diseases (AI 24136)
National Institute of Dental and Craniofacial Research (DE10913)
Topics: Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Physical Sciences › Environmental Science › Pollution › Pharmaceutical and Antibiotic Environmental Impacts
Keywords: tetracycline resistance, antibiotic resistance determinants, efflux pumps, gene expression regulation, transposable elements, mobile genetic elements, plasmids, gene transfer, reservoir of resistance genes, Gram-negative bacteria, Gram-positive bacteria, antibiotic use in agriculture, Shigella dysenteriae
MeSH terms: Animals, Bacteria, Bacterial Proteins, Carrier Proteins, Genes, Bacterial, Gram-Negative Bacteria, Gram-Positive Bacteria, Humans, Molecular Sequence Data, Ribosomes, Tetracycline, Tetracycline Resistance, Gene Expression Regulation, Bacterial

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Tetracycline resistance determinants: mechanisms of action, regulation of expression, genetic mobility, and distribution

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