Can Vet J. 2002 Dec;43(12):940-5.
An evaluation of the relative efficacy of a new formulation of oxytetracycline for the treatment of undifferentiated fever in feedlot calves in western Canada.

Schunicht OC, Booker CW, Guichon PT, Jim GK, Wildman BK, Hill BW, Ward TI, Bauck SW.

Feedlot Health Management Services, Bay 7-87 Elizabeth Street, Postal Bag Service #5, Okotoks, Alberta T0L 1T0.

A field trial was performed under commercial feedlot conditions in western Canada to compare the efficacy of a new formulation of long-acting oxytetracycline (LA 30) to a standard long-acting oxytetracycline formulation (LA 20) and florfenicol (FLOR) for the treatment of undifferentiated fever (UF) in calves that received metaphylactic tilmicosin upon arrival at the feed-lot. Seven hundred and ninety-seven recently weaned, auction market derived, crossbred, beef calves suffering from UF were allocated to 1 of 3 experimental groups as follows: LA 30, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at the rate of 30 mg/kg body weight (BW) at the time of allocation; LA 20, which received intramuscular long-acting oxytetracycline (200 mg/mL formulation) at the rate of 20 mg/kg BW at the time of allocation; or FLOR, which received intramuscular florfenicol administered at the rate of 20 mg/kg BW at the time of allocation and again 48 hours later. Two hundred and sixty-six animals were allocated to the LA 30 group, 265 animals were allocated to the LA 20 group, and 266 animals were allocated to the FLOR group. The relative efficacy of the LA 30 group, as compared with the LA 20 and FLOR groups, was assessed by comparing relapse, chronicity, wastage, and mortality rates. The overall mortality (RR = 0.50) rate in the LA 30 group was significantly (P < 0.05) lower than in the LA 20 group. However, the overall chronicity (RR = 2.56) and overall wastage (RR = 6.97) rates of the LA 30 group were significantly (P < 0.05) higher than in the LA 20 group. There were no significant (P > or = 0.05) differences in UF relapse rates or cause specific mortality rates between the LA 30 and LA 20 groups. In the economic analysis, there was an advantage of $28.59 CDN per animal in the LA 30 group compared with the LA 20 group. The overall chronicity (RR = 2.25) and overall wastage (RR = 2.80) rates of the LA 30 group were significantly (P < 0.05) higher than the FLOR group. There were no significant (P > or = 0.05) differences in UF relapse rates, overall mortality rates, or cause specific mortality rates between the LA 30 and FLOR groups. In the economic analysis, there was an advantage of $12.90 CDN per animal in the LA 30 group compared with the FLOR group. In summary, the results of this study indicate that it is more cost-effective to use a new formulation of long-acting oxytetracycline (300 mg/mL formulation administered at a rate of 30 mg/kg BW) than a standard long-acting oxytetracycline formulation (200 mg/mL formulation administered at a rate of 20 mg/kg BW) or florfenicol for the treatment of UF in feedlot calves that have previously received metaphylactic tilmicosin upon arrival at the feedlot.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12561688&dopt=Abstract antibiotics, tetracycline

eastman.ucl.ac.uk

The aim of this study was to investigate the effects of tetracycline administration on the viability and antibiotic resistance profiles of microcosm dental plaques. A constant depth film fermenter was used to generate multi-species biofilms, which were grown for 216 h before tetracycline was added. The composition of the microcosm plaques was determined by viable counting on selective and non-selective media. The prevalence of antibiotic-resistant organisms was determined on antibiotic-containing media. Before administration of tetracycline, the biofilms had a total viable anaerobic count of 7 x 10(7) cfu per biofilm. They contained 7% lactobacilli, 19% streptococci and 2% Actinomyces spp. Immediately after pulsing with tetracycline, the composition of the biofilms changed and they consisted of 30% lactobacilli, 1.5% streptococci and 3% Actinomyces spp., with a total anaerobic count of 1 x 10(7) cfu per biofilm. The pre-valence and composition of the antibiotic-resistant microflora changed dramatically after the addition of tetracycline, with the proportion of the microflora displaying resistance to tetracycline increasing from 6% to 45%. Corresponding changes in the proportions of the microflora displaying resistance to other antibiotics were as follows: 5-28% for erythromycin, 1-5% for vancomycin and 0.4-3% for ampicillin. The results of this study have shown that the addition of tetracycline to microcosm dental plaques alters their composition and enriches for bacteria resistant to tetracycline and other unrelated agents.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12003970&dopt=Abstract antibiotics, tetracycline




Antimicrob Agents Chemother. 2003 Mar;47(3):878-82.
Prevalence of tetracycline resistance genes in oral bacteria.

Villedieu A, Diaz-Torres ML, Hunt N, McNab R, Spratt DA, Wilson M, Mullany P.

Eastman Dental Institute, Department of Microbiology, University College London, United Kingdom.

Tetracycline is a broad-spectrum antibiotic used in humans, animals, and aquaculture; therefore, many bacteria from different ecosystems are exposed to this antibiotic. In order to determine the genetic basis for resistance to tetracycline in bacteria from the oral cavity, saliva and dental plaque samples were obtained from 20 healthy adults who had not taken antibiotics during the previous 3 months. The samples were screened for the presence of bacteria resistant to tetracycline, and the tetracycline resistance genes in these isolates were identified by multiplex PCR and DNA sequencing. Tetracycline-resistant bacteria constituted an average of 11% of the total cultivable oral microflora. A representative 105 tetracycline-resistant isolates from the 20 samples were investigated; most of the isolates carried tetracycline resistance genes encoding a ribosomal protection protein. The most common tet gene identified was tet(M), which was found in 79% of all the isolates. The second most common gene identified was tet(W), which was found in 21% of all the isolates, followed by tet(O) and tet(Q) (10.5 and 9.5% of the isolates, respectively) and then tet(S) (2.8% of the isolates). Tetracycline resistance genes encoding an efflux protein were detected in 4.8% of all the tetracycline-resistant isolates; 2.8% of the isolates had tet(L) and 1% carried tet(A) and tet(K) each. The results have shown that a variety of tetracycline resistance genes are present in the oral microflora of healthy adults. This is the first report of tet(W) in oral bacteria and the first report to show that tet(O), tet(Q), tet(A), and tet(S) can be found in some oral species.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12604515&dopt=Abstract antibiotics, tetracycline




J Bacteriol. 1989 Jan;171(1):148-53.
Novel aerobic tetracycline resistance gene that chemically modifies tetracycline.

Speer BS, Salyers AA.

Department of Microbiology, University of Illinois, Urbana 61801.

A tetracycline resistance gene that was found originally on the Bacteroides plasmid pBF4 confers resistance on Escherichia coli but only when cells are growing aerobically. When E. coli EM24 carrying this aerobic tetracycline resistance (*Tcr) gene is grown in medium containing tetracycline, the resulting spent medium is no longer toxic to tetracycline-sensitive (Tcs) E. coli EM24 (B.S. Speer and A.A. Salyers, J. Bacteriol. 170: 1423-1429, 1988). To determine whether the *Tcr gene product modified tetracycline, we characterized the material resulting from incubation of E. coli (*Tcr) with tetracycline. When [7-3H(N)]tetracycline was added to cultures of E. coli (*Tcr), at least 90% of the label was recovered in the extracellular fluid. Therefore, tetracycline was not being sequestered by the cells. The labeled material behaved similarly to tetracycline with respect to solubility in various organic solvents. However, the UV-visible light spectrum had a single peak at 258 nm, whereas the tetracycline spectrum had a peak at 364 nm. The labeled material also had a faster migration rate than did tetracycline on thin-layer plates in a solvent system of butanol-methanol-10% citric acid (4:1:2, vol/vol/vol) and was separable from tetracycline by reverse-phase high-pressure liquid chromatography, using an acetronitrile-0.1% trifluoroacetic acid solvent system. These results demonstrate that the *Tcr gene product chemically modifies tetracycline. The *Tcr gene is the first example of a chemically modifying tetracycline resistance mechanism.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2644186&dopt=Abstract antibiotics, tetracycline




J Bacteriol. 1986 Feb;165(2):564-9.
Streptococcal tetracycline resistance mediated at the level of protein synthesis.

Burdett V.

The mechanism of tetracycline resistance was examined in strains containing each of the three previously identified resistance determinants in Streptococcus spp. Uptake of tetracycline was measured in tetracycline-sensitive cells as well as in cells containing each of the three resistance determinants. In cells containing tetL, uptake was not observed. However, in sensitive cells and cells containing either tetM or tetN, tetracycline was accumulated approximately 25-fold against a concentration gradient. Furthermore, there was no evidence for modification of intracellular tetracycline recovered from sensitive, tetM, or tetN cells. Protein synthesis in extracts derived from organisms containing tetM or tetN was resistant to tetracycline. In contrast, extracts of sensitive and tetL cells were sensitive to tetracycline.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3080409&dopt=Abstract antibiotics, tetracycline




Mol Gen Genet. 1979 Jan 10;168(2):173-84.
Repetition of tetracycline resistance determinant genes on R plasmid pRSD1 in Escherichia coli.

Mattes R, Burkardt HJ, Schmitt R.

The 30 megadalton (Mdal)-conjugative, fi- plasmid pRSD1 determines inducible tetracycline resistance (Tc) in Escherichia coli. As shown by restriction analysis, a 3.5 Mdal-EcoRI fragment of pRSD1 spliced into the small plasmid pRSD2124 comprises the entire Tc determinant (tet) region. A restriction map of pRSD1 is presented which includes the location of the tet region and of an "underwound" loop not related to Tc (Burkardt et al., 1978). Selective amplification of tet genes is demonstrated by three lines of evidence. (i) The resistance level of cell harbouring pRSD1 increases approximately tenfold by induction with 10 microgram/ml of tetracycline. Further growth in the presence of 100 microgram/ml of the drug ("tetracycline stress") selects for cells with even higher resistance levels (about 300 microgram/ml) in rec+ cells. In a recA strain, a smaller proportion of cells attains these high resistance levels suggesting the involvement of host recombination. (ii) Electron micrographs of pRSD1-DNA isolated from tetracycline-stressed cells reveal a heterogeneous population of circular DNA molecules ranging between 1.7 and 21.6 micron. The distribution of contour lengths shows a discrete pattern ascribed to the presence of autonomous single- and multiple-copy Tc determinants and to intact plasmids containing zero to six tet regions in tandem repeats. (iii) This interpretation is supported by heteroduplex and restriction analyses which demonstrate the presence of multiple copies of the 3.5 Mdal-element encompassing the tet region in pRSD1 molecules selected by tetracycline stress. It has been concluded that gene amplification leading to tandem repetition of the tet region ensues in pRSD1. Such plasmids confer increased tetracycline resistance and can, thefore, be selected by high doses of the drug.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=377009&dopt=Abstract antibiotics, tetracycline




Plant Mol Biol. 1996 Jan;30(1):199-205.
Tetracycline-regulated reporter gene expression in the moss Physcomitrella patens.

Zeidler M, Gatz C, Hartmann E, Hughes J.

Institut fur Pflanzenphysiologie, Freie Universitat Berlin, Germany.

As ancestors of higher plants, mosses offer advantages as simple model organisms in studying complex processes such as development and signal transduction. Overexpression of transgenes after genetic transformation is a powerful technique in such studies. To establish a controllable expression system for this experimental approach we expressed a chimeric protein consisting of the Tn1O-encoded Tet repressor and the activation domain of Herpes simplex virion protein 16 in the moss Physcomitrella patens. We showed that this protein activates transcription from a suitable target promoter (Top 1O) containing seven operators upstream of a TATA box. In media containing very low levels of tetracycline (1 mg/l), expression levels of a beta-glucuronidase (GUS) reporter gene dropped to <1% of that in the absence of tetracycline. This regulation is due to interference of tetracycline with the DNA binding activity of the Tet repressor portion of the chimeric transcriptional activator. Stable transformants grown for three weeks on tetracycline-containing media showed negligible GUS activity, whereas GUS was expressed strongly within 24 h of transfer to tetracycline-free media. Potent and stringently regulated expression of other, physiologically active genes is thus readily available in the moss system using the convenient ToplO expression system.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8616238&dopt=Abstract antibiotics, tetracycline




Gene Ther. 1999 Mar;6(3):309-13.
Control of parvovirus DNA replication by a tetracycline-regulated repressor.

Maxwell IH, Maxwell F.

University of Colorado Cancer Center, Denver 80262, USA.

Autonomous parvoviruses are small, single strand DNA viruses which preferentially replicate in transformed and tumor cells, causing cell death by expression of the cytotoxic nonstructural protein, NS1. Several parvoviruses of the rodent group, including LuIII, efficiently infect human transformed cell lines. The potential for systemic use of these viruses in targeting metastases might be enhanced if NS1 expression and viral replication could be controlled by an innocuous drug such as tetracycline. We therefore substituted prokaryotic tetracycline operator sequences for part of P4 of LuIII, the promoter responsible for transcription of the mRNAs for nonstructural proteins. The resulting construct unexpectedly showed constitutive expression in transiently transfected cells, as indicated by efficient excision and amplification of viral replicative form (RF) DNA. This was apparently due to self-stimulatory transcriptional transactivation by NS1. This problem was overcome by cotransfection with a plasmid expressing a chimera of the repressor of the tetracycline operon with a KRAB transrepression domain. These conditions allowed efficient control of transcription and RF amplification by the tetracycline derivative, doxycycline. These observations form a basis for developing a therapeutic agent based on a drug-controlled parvovirus.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10435080&dopt=Abstract antibiotics, tetracycline