Biol Chem. 1998 Jul;379(7):847-55.
Ribosomal protection from tetracycline mediated by Tet(O): Tet(O) interaction with ribosomes is GTP-dependent.

Trieber CA, Burkhardt N, Nierhaus KH, Taylor DE.

Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.

Tet(O) mediates tetracycline resistance by protecting the ribosome from inhibition. A recombinant Tet(O) protein with a histidine tag was purified and its activity in protein synthesis characterized. Tetracycline inhibited the rate of poly(Phe) synthesis, producing short peptide chains. Tet(O)-His was able to restore the elongation rate and processivity. 70S ribosomes bound tetracycline with high affinity. Tet(O)-His in the presence of GTP, but not GDP or GMP, reduced the affinity of the ribosomes for tetracycline. Non-hydrolyzable GTP analogs in the presence of the factor were also able to interfere with tetracycline binding. Ribosomes increased the affinity of Tet(O)-His for GTPgammaS. Tet(O), 70S ribosomes and GTPgammaS formed a complex that could be isolated by gel filtration. The GTP conformer is the active form of Tet(O) that interacts with the ribosome. GTP binding is necessary for Tet(O) activity.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9705148&dopt=Abstract antibiotics, tetracycline




Gastroenterology. 1975 Sep;69(3):714-23.
Fatty liver induced by tetracycline in the rat. Dose-response relationships and effect of sex.

Breen KJ, Schenker S, Heimberg M.

Dose-response relationships, biochemical mechanisms, and sex differences in the experimental fatty liver induced by tetracycline were studied in the intact rat and with the isolated perfused rat liver in vitro. In the intact male and female rat, no direct relationship was observed between dose of tetracycline and hepatic accumulation of triglyceride. With provision of adequate oleic acid as a substrate for the isolated perfused liver, a direct relationship was observed between dose of tetracycline and both accumulation of triglyceride in the liver and depression of output of triglyceride by livers from male and female rats. Marked differences were observed between female and male rats with regard to base line (control) hepatic concentration of triglyceride and output of triglyceride. Accumulation of hepatic triglyceride, as a per cent of control values, in response to graded doses of tetracycline, did not differ significantly between male, female and pregnant rat livers. However, livers from female, and especially pregnant female rats, were strikingly resistant to the effects of tetracycline on depression of output of triglyceride under these experimental conditions. These differences between the sexes could not be related to altered disposition of tetracycline or altered uptake of oleic acid. Depressed hepatic secretion of triglyceride accounted only for 30 to 50% of accumulated hepatic triglyceride, indicating that additional mechanisms must be involved in the production of the triglyceride-rich fatty liver in response to tetracycline.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1158089&dopt=Abstract antibiotics, tetracycline




J Dairy Sci. 2002 Mar;85(3):487-93.
Rapid determination of tetracycline in milk by FT-MIR and FT-NIR spectroscopy.

Sivakesava S, Irudayaraj J.

Department of Agricultural and Biological Engineering, The Pennsylvania State University, University Park 16802, USA.

The feasibility of measuring tetracycline at the ppb levels in milk was investigated by Fourier transform mid-infrared (FT-MIR) and Fourier transform near-infrared (FT-NIR) spectroscopic techniques. Milk samples spiked with different concentrations of tetracycline were scanned using FT-MIR and FT-NIR spectroscopy. Suitable spectral wave number regions were selected for principal least square (PLS) regression models development. Prediction errors were high when the calibration model was developed using the wide range of tetracycline concentrations (4 to 2000 ppb) in milk. Maximum correlation coefficient (R2) value of about 0.89 was obtained for the validation models developed using different concentration ranges. Prediction errors were high for FT-NIR method. Results indicated that FT-MIR spectroscopy could be used for rapid detection of tetracycline hydrochloride residues in milk.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11949850&dopt=Abstract antibiotics, tetracycline




J Agric Food Chem. 2002 Aug 14;50(17):4812-5.
Detection of traces of tetracyclines from fish with a bioluminescent sensor strain incorporating bacterial luciferase reporter genes.

Pellinen T, Bylund G, Virta M, Niemi A, Karp M.

Department of Biotechnology, University of Turku, Tykistokatu 6A, FIN-20520 Turku, Finland.

Bioluminescent Escherichia coli K-12 strain for the specific detection of the tetracycline family of antimicrobial agents was optimized to work with fish samples. The biosensing strain contains a plasmid incorporating the bacterial luciferase operon of Photorhabdus luminescens under the control of the tetracycline responsive element from transposon Tn10 (Korpela et al. Anal. Chem. 1998, 70, 4457-4462). The extraction procedure of oxytetracycline from rainbow trout (Oncorhynchus mykiss) tissue was optimized. There was neither need for centrifugation of homogenized tissue nor use of organic solvents. The lowest levels of detection of tetracycline and oxytetracycline from spiked fish tissue were 20 and 50 microg/kg, respectively, in a 2-h assay. The optimized assay protocol was tested with fish that were given a single oral dose of high and low concentrations of oxytetracycline. The assay was able to detect oxytetracycline residues below the European Union maximum residue limits, and the results correlated well with those obtained by conventional HPLC (R = 0.81).

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12166964&dopt=Abstract antibiotics, tetracycline




J Antibiot (Tokyo). 1992 Dec;45(12):1892-8.
Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. I. Taxonomy, production, isolation and biological activity.

Wells JS, O'Sullivan J, Aklonis C, Ax HA, Tymiak AA, Kirsch DR, Trejo WH, Principe P.

Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.

A screen for antibiotics with activity against tetracycline-resistant microorganisms has led to the isolation of Dactylosporangium sp. (ATCC 53693), a producer of several novel tetracycline derivatives. The major fermentation products, dactylocyclines A and B, were purified and MIC values determined against tetracycline-resistant and tetracycline-sensitive Gram-positive bacteria. The dactylocyclines represent the first naturally occurring tetracycline C2 amides which lack cross resistance with tetracycline.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1490880&dopt=Abstract antibiotics, tetracycline




J Antibiot (Tokyo). 1992 Dec;45(12):1899-906.
Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. II. Structure elucidation.

Tymiak AA, Ax HA, Bolgar MS, Kahle AD, Porubcan MA, Andersen NH.

Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.

Fermentation of Dactylosporangium sp. (ATCC 53693) produces a mixture of tetracycline derivatives from which several related tetracycline glycosides, the dactylocyclines, were isolated and their structures determined. The most abundant glycoside in initial fermentations was found to be dactylocycline A. Each glycoside proved to be acid sensitive and readily hydrolyzed to a common aglycone, dactylocyclinone. While the aglycone was cross resistant with tetracycline, the dactylocyclines proved active against certain tetracycline-resistant organisms.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1490881&dopt=Abstract antibiotics, tetracycline




J Clin Pharmacol. 1989 Aug;29(8):748-51.
Impaired absorption of tetracycline by colestipol is not reversed by orange juice.

Friedman H, Greenblatt DJ, LeDuc BW.

Upjohn Company, Kalamazoo, MI.

Nine volunteers received a 500 mg oral dose of tetracycline hydrochloride in three trials: A: With 180 ml water; B: With 30 gm colestipol in 180 ml water; C: With 30 gm colestipol in 180 ml orange juice. Tetracycline concentrations in multiple urine samples collected during 48 hours after each dose were determined by high pressure liquid chromatography. The three trials did not differ significantly in 48 hour cumulative urine volume (3086 vs 3207 vs 3194 ml for Trials A, B, and C). However, the three trials differed significantly in 48 hour excretion of tetracycline (F = 28.2; P less than .001). During Trial A, mean excretion was 237 mg; this was significantly (P less than .05) reduced to 109 mg in Trial B and 104 mg in Trial C. However, Trials B and C were not different. Thus, coadministration of tetracycline with colestipol significantly impairs tetracycline absorption by more than 50%. Mixing colestipol with orange juice does not alter colestipol-induced impairment of tetracycline absorption.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2778097&dopt=Abstract antibiotics, tetracycline




Biochim Biophys Acta. 1988 Jan 25;949(1):49-57.
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.

Department of Life Science, Faculty of Science, Tokyo Institute of Technology, Yokohama, Japan.

Bacillus subtilis GSY908 DNA fragments (5.1 and 4.4 kilobase pairs (kb)) containing a tetracycline-resistance determinant were cloned in Escherichia coli using a shuttle plasmid vector pLS353. Restriction endonucelase analysis showed that the 4.4 kb fragment is a spontaneous deletion derivative of the 5.1 kb fragment. E. coli tetracycline-resistance transformants carrying pLS353 with the 5.1 kb fragment (named pTBS1) and that with 4.4 kb fragment (pTBS1.1) could grow at tetracycline concentrations up to 80 and 50 micrograms per ml, respectively. B. subtilis MI112 and RM125 were transformed by pTBS1, resulting in isolation of transformants of MI112 maintaining pTBS1 and RM125 maintaining either pTBS1 or pTBS1.1. Maximum tetracycline concentrations permitting growth of plasmidless MI112 and MI112 with pTBS1 were 4 and 10 micrograms per ml, respectively, while those of plasmidless RM125, RM125 with pTBS1 and RM125 with pTBS1.1 were 7, 50 and 80 micrograms per ml, respectively. It was interesting to note that the tetracycline-resistance level in E. coli conferred by the 5.1 kb fragment is higher than that conferred by the 4.4 kb fragment, but in B. subtilis the 4.4 kb fragment, in contrast, confers a higher level of tetracycline resistance. The level of tetracycline resistance in B. subtilis conferred by the cloned determinant clearly depends on the host strain. The tetracycline resistance conferred by the cloned determinant was associated with decreased accumulation of the drug into the cells. However, it was constitutive in E. coli, but inducible in B. subtilis. The cloned tetracycline-resistance determinant was detected specifically on the chromosome of B. subtilis Marburg 168 derivatives.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2825813&dopt=Abstract antibiotics, tetracycline