FEBS Lett. 1995 May 29;365(2-3):193-7.
The tetracycline efflux protein encoded by the tet(K) gene from Staphylococcus aureus is a metal-tetracycline/H+ antiporter.

Yamaguchi A, Shiina Y, Fujihira E, Sawai T, Noguchi N, Sasatsu M.

Division of Microbial Chemistry, Faculty of Pharmaceutical Sciences, Chiba University, Japan.

The tet(K) gene from Staphylococcus aureus was highly expressed in Escherichia coli by an alteration of its initiation codon from TTG to ATG and its ribosome-binding sequence from GAGG to GGAGG [Noguchi, N. et al. (1994) Biol. Pharm. Bull. 17, 352-355]. The inverted membrane vesicles prepared from the tet(K)-expressing cells showed respiration-dependent [3H]tetracycline transport comparable to the vesicles from the tet(B)-expressing cells. The affinity of Tet(K) vesicles to tetracycline was the same as that of Tet(B) vesicles, whereas the former Vmax value was about 60% of the latter one. Contrary to Tet(B) vesicles, Tet(K) vesicles showed no significant minocycline uptake, which was consistent with the low minocycline resistance of the Tet(K)-producing cells. The tetracycline transport mediated by Tet(K) vesicles was coupled with proton transport and the translocation of 60Co2+ ions as well as in Tet(B) vesicles. This observation indicates that the class K tetracycline resistance determinant from Gram-positive bacteria also encodes a metal-tetracycline/H+ antiporter that is functionally similar to that encoded by tet(B), although there is a considerable difference in the primary sequences and the putative topologies of these Tet proteins.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7781778&dopt=Abstract antibiotics, tetracycline




J Bacteriol. 1984 Apr;158(1):49-54.
Streptococcus faecalis proton gradients and tetracycline transport.

Munske GR, Lindley EV, Magnuson JA.

The transport of chlortetracycline by Streptococcus faecalis is energy dependent. Addition of glucose to energy-depleted cells enhances both the transport rates and accumulation levels. Transport rates can be altered independently of glucose by treating cells with ionophores that increase or decrease the proton gradient. The transport of the antibiotic is linked only to the transmembrane pH difference, delta pH, and not the transmembrane electrical potential, delta psi. This conclusion was verified by quantitative measurements of delta pH, delta psi, and tetracycline accumulation levels. A linear correlation between delta pH and the tetracycline electrochemical potential was observed. Tetracycline most likely accumulates by the symport of protons in which the protons are bound to an anionic form of the antibiotic to form an uncharged molecule.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6325398&dopt=Abstract antibiotics, tetracycline




Oral Microbiol Immunol. 1996 Oct;11(5):304-8.
Tetracycline resistance in Prevotella isolates from periodontally diseased patients is due to the tet(Q) gene.

Olsvik B, Flynn MJ, Tenover FC, Slots J, Olsen I.

University of Oslo, Norway.

Tetracycline-resistance in gram-negative periodontal bacteria is often due to the presence of the tet(Q) gene. In the present study the polymerase chain reaction (PCR) was used to examine 54 isolates of gram-negative anaerobic rods (Prevotella intermedia, Prevotella nigrescens and related or Bacteroides-like species) for the presence of the tet(Q) gene. The isolates were recovered from 42 patients with periodontal disease living in northern Europe and North America. An 814 base-pair segment of the tet(Q) gene was amplified from all 41 isolates resistant to tetracycline with minimal inhibitory concentrations of 4 micrograms/ml and above. The presence of the tet(Q) gene was verified using hybridization with a specific oligonucleotide internal to the amplified region and restriction endonuclease digestion with DdeI. A PCR product of the same size was also amplified from one tetracycline susceptible isolate (minimal inhibitory concentration = 0.5 microgram/ml). However, this isolate and the one isolate that was resistant to tetracycline at 4 micrograms/ml showed a weaker signal than the remaining isolates when hybridized with the internal probe. Typing of the PCR products using restriction endonuclease digests with AluI and HpaII revealed two clusters of distinct electrophoresis patterns, indicating that two different subtypes of the tet(Q) gene were present in this material. A control strain containing the tet(Q) gene from Bacteroides thetaiotaomicron had a different electrophoresis pattern for AluI. This study indicated that subtypes of the tet(Q) gene in tetracycline-resistant gram-negative periodontal bacteria exist both within the same patient and within the same species.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9028255&dopt=Abstract antibiotics, tetracycline




Jpn J Antibiot. 1982 May;35(5):1233-9.
[Susceptibilities of Pseudomonas species to aminoglycosides and tetracyclines]

[Article in Japanese]

Igari J, Kosakai N, Oguri T.

Pseudomonas aeruginosa has attracted much attention through its role in hospital outbreaks of disease. However, other members of the genus Pseudomonas, particularly Pseudomonas maltophilia and Pseudomonas cepacia, may be isolated as opportunistic pathogens of man, and can be found in hospital materials. These organisms have been less susceptible to the commonly used antibiotics. This report deals with the in vitro sensitivity of Pseudomonas strains except for P. aeruginosa to aminoglycosides and tetracyclines. The following bacteria were tested: P. maltophilia (50 strains), P. fluorescens (29 strains), P. putida (52 strains), P. cepacia (49 strains), P. putrefaciens (18 strains), P. acidovorans (12 strains). All of the strains for this study were isolated from routine cultures of infected clinical materials which sent to the Clinical Laboratories, Juntendo University Hospital during the 1 year period of 1980. The tests for susceptibility of the strains to the 3 aminoglycosides (gentamicin, tobramycin, amikacin) and 3 tetracyclines (tetracycline, doxycycline, minocycline) were all performed by the serial 2-fold agar plate dilution method on heart infusion agar, standardized by the Japan Society of Chemotherapy, using the microplanter apparatus with an inoculum size of approximately 10(8) CFU/ml. There were similar sensitivity patterns for the aminoglycosides tested; most of the strains of P. maltophilia, P. cepacia and P. acidovorans were resistant to the aminoglycosides, while most of P. fluorescens, P. putida and P. putrefaciens were sensitive. Minocycline and doxycycline were extremely active to the Pseudomonas species studied. Tetracycline was almost ineffective against P. maltophilia and P. cepacia.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7131756&dopt=Abstract antibiotics, tetracycline




Anal Biochem. 1998 Jun 1;259(2):187-94.
A single plasmid vector (pSTAR) mediating efficient tetracycline-induced gene expression.

Zeng Q, Tan YH, Hong W.

Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore, 117609, Singapore.

A plasmid vector (pSTAR) has been constructed which confers neomycin resistance for selecting stably transfected cells, possesses a cloning cassette for placing a gene of interest under the control of the tetO DNA motif, and expresses rtTAnls which, upon association with tetracycline, binds to and drives gene expression from the tetO DNA motif. The plasmid pSTAR/LacZ, which has the gene for beta-galactosidase inserted into the cloning cassette, was transfected into Chinese hamster ovary (CHO) cells and selected for stably transfected cells. In pooled transfectants of CHO, tetracycline induced the expression of beta-galactosidase in 10-30% of cells. Using clonal transfectants, beta-galactosidase expression was induced by tetracycline in essentially every cell. Furthermore, induction of beta-galactosidase expression by tetracycline was both dose- and time-dependent. Similar tetracycline-induced beta-galactosidase expression is also observed in other cell types. The pSTAR vector is thus suited to facilitate the application of tetracycline-induced gene expression in diverse research areas. Copyright 1998 Academic Press.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9618196&dopt=Abstract antibiotics, tetracycline




J Antimicrob Chemother. 1996 May;37(5):1005-9.
In-vitro activity of psychiatric drugs against Corynebacterium urealyticum (Corynebacterium group D2).

Munoz-Bellido JL, Munoz-Criado S, Garcia-Rodriguez JA.

Departamento de Microbiologia y Parasitologia, Hospital Universitario de Salamanca, Spain.

We tested the in-vitro activity of amoxycillin, amoxycillin/clavulanic acid, cefotaxime, gentamicin, trimethoprim-sulphamethoxazole, tetracycline, norfloxacin, ciprofloxacin, vancomycin, teicoplanin, clindamycin and five psychiatric drugs (chlorpromazine, sertraline, fluoxetine, paroxetine and risperidone) against 32 strains of Corynebacterium urealyticum. Resistance rates exceeded 90% for all antibiotics except glycopeptides, quinolones and tetracycline. Sertraline was the most active psychiatric drug. We tested the influence of sertraline on the activity of amoxycillin, amoxycillin/clavulanic acid, cefotaxime, gentamicin, trimethoprim-sulphamethoxazole, tetracycline and ciprofloxacin. We did not observe antagonism in any case. Sertraline enhanced the activity of ciprofloxacin and tetracycline against all strains (MIC decrease: 4-64-fold for ciprofloxacin, 2-32-fold for tetracycline).

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8737151&dopt=Abstract antibiotics, tetracycline




Pharm Dev Technol. 2003 Aug;8(3):253-62.
Stomach-specific anti-H. pylori therapy. II. Gastric residence studies of tetracycline-loaded chitosan microspheres in gerbils.

Hejazi R, Amiji M.

Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts 02115, USA.

This study examines the gastric residence of chitosan microspheres and the local tetracycline concentrations following oral administration in gerbils. Chitosan microspheres were prepared by ionic cross-linking and precipitation with sodium sulfate. Gastric retention studies were performed by administering radioiodinated [125I] chitosan microsphere suspension in the nonacid-suppressed and acid-suppressed states. At different time points, animals were sacrificed, and the radioactivity in tissues and fluids was measured with a gamma counter. Local tetracycline concentrations were measured using chitosan microspheres loaded with tritiated-[3H]-tetracycline. The radioactivity, measured with a liquid scintillation analyzer, was used to determine the microg of drug per gram of tissues or fluids under nonacid-suppressed and acid-suppressed states. Microspheres with a spherical shape and an average diameter of 2.0-3.0 microm were formed. After 2 hr in the fasted stomach, approximately 10% of the administered dose remained. The microspheres were predominantly found in the colon after 6 hr of administration. There was no detectable radioactivity in the small intestine, plasma, urine, liver, and kidneys. Additionally, acid suppression with ranitidine did not influence the gastric residence time of chitosan microspheres. To our disappointment, tetracycline concentration profile in the stomach from microsphere formulation was similar to the aqueous solution. Also, there was no significant difference between the stomach tetracycline concentrations in the nonacid-suppressed and acid-suppressed states. The drug was predominantly found in the colon and urine samples after 6 hr. Tetracycline could not be detected in the plasma, small intestine, liver, or kidneys. Results of this study show that chitosan microspheres prepared by ionic cross-linking do not provide a longer residence time in the fasted gerbil stomach. The tetracycline concentration profile in the stomach, following administration in microsphere formulation, was similar to that of aqueous solution. Lastly, acid suppression did not influence the gastric residence time of chitosan microspheres or tetracycline concentration profiles.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12901691&dopt=Abstract [PubMed - in process]




Arzneimittelforschung. 1979;29(11):1693-5.
Distribution of pyrrolidinomethyl-tetracycline (rolitetracycline) and tetracycline in blood and various organs of mice measured by high pressure liquid chromatography.

Bocker R, Estler CJ.

By means of a newly developed high-pressure liquid chromatographic method the organ distribution of tetracycline (TC) and pyrrolidinomethyl-tetracycline (PMT) has been studied. When mice were treated with 50 mg/kg i.v. TC or PMT these antibiotics could be detected in all organs investigated (liver, kidney, heart, lung, muscle, spleen). Especially high concentrations were found in liver and kidneys, where TC and PMT could be detected up to 6 h. In animals treated with PMT part of the PMT applied decomposed slowly yielding TC, which was found together with PMT in blood and all organs.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=543877&dopt=Abstract antibiotics, tetracycline