Concept: Tetracycline antibiotics
In recent years, tetracyclines, such as doxycycline, have become broadly used to control gene expression by virtue of the Tet-on/Tet-off systems. However, the wide range of direct effects of tetracycline use has not been fully appreciated. We show here that these antibiotics induce a mitonuclear protein imbalance through their effects on mitochondrial translation, an effect that likely reflects the evolutionary relationship between mitochondria and proteobacteria. Even at low concentrations, tetracyclines induce mitochondrial proteotoxic stress, leading to changes in nuclear gene expression and altered mitochondrial dynamics and function in commonly used cell types, as well as worms, flies, mice, and plants. Given that tetracyclines are so widely applied in research, scientists should be aware of their potentially confounding effects on experimental results. Furthermore, these results caution against extensive use of tetracyclines in livestock due to potential downstream impacts on the environment and human health.
Abstract Background The oral tetracyclines, especially minocycline hydrochloride, are often used as an effective treatment for perioral dermatitis, however they are sometimes difficult to use because of the side effects, especially in children. Objective The effectiveness of β-lactam antibiotics was evaluated in three cases of perioral dermatitis. Methods Three Japanese patients with perioral dermatitis were treated with cefcapene pivoxil hydrochloride hydrate per os 100 to 300 mg per day. They were one girl (age 10) and two adult women (age 32, 37). One of the adult patients had a past history of Meniere’s disease and the other had had a side effect, vertigo, from minocycline hydrochloride treatment. The presence of fusobacteria before and after the treatment was examined using the tape-stripping toluidine blue method. Results These patients showed the improvement in 1 to 2 weeks and were much improved or cured after 2 to 5 weeks. No side effects were found during the treatment. Fusobacteria were positive before treatment but became negative after the treatment in all of them. Conclusion β-lactam antibiotics might be a useful treatment for perioral dermatitis, especially in cases who cannot take tetracyclines.
Antibiotics (sulfonamides and tetracyclines) have attractive increasing attention due to their persistence for a long time, which lead to concern of widespread antibiotic resistant bacteria and resistance genes in the aquatic environment. Investigation of the occurrence and elimination of antibiotics in the wastewater treatment plant (WWTP) effluent is thus imperative. This paper presents the method development of the liquid chromatography-ion-trap mass spectrometer (IT-MS)-time-of-flight mass spectrometer in series (LC-IT-ToF/MS) hybrid technique to determine concentrations of sulfonamides and tetracyclines in the effluent of animal WWTP. Detection limits of the developed method were 22.8, 23.0, 25.8, 23.6, and 9.8ngL(-1) for sulfathiazole, sulfamethazine, sulfamethoxazole, oxytetracycline, and chlortetracycline, respectively. Average recovery efficiencies of the method for sulfonamides fortified in effluent samples of ananimal WWTP at 1.0, and 4.0μgL(-1) were 73-95%, and 89-104%, respectively, while that of the method for tetracyclines fortified at 0.4 and 4.0μgL(-1) was 76-104%, and 101-107%, respectively. The analysis of effluent of the WWTP showed that more than 90% of analyzed antibiotics were removed by the treatment consisted of biological, a UF membrane, and a coagulation process. The maximum concentrations of sulfonamide and tetracycline in the WWTP were 49.5 and 4.1μgL(-1), respectively.
High-performance liquid chromatography using pressurized liquid extraction for the determination of seven tetracyclines in egg, fish and shrimp
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
- Published over 5 years ago
A simple and especially rapid method, pressurized liquid extraction, has been developed and applied to the quantitative determination of oxytetracycline, tetracycline, chlortetracycline, minocycline, methacycline, demeclocycline and doxycycline in egg, fish and shrimp. The procedure consisted of a trichloracetic acid/methanol extraction conducted at elevated temperature (60°C) and pressure (65bar), without further clean-up, the extraction solution was concentrated and finally for high-performance liquid chromatography analysis. The limits of detection were 5.0-10.0μg/kg and the limits of quantification were 10.0-15.0μg/kg for tetracyclines in egg, fish and shrimp using UV detection. The analytical limits CCα and CCβ were also calculated. The recoveries of tetracyclines spiked at levels of 15-300μg/kg, averaged 75.6-103.5% with the relative standard deviation values less than 11%. The optimized procedure has been successfully applied to real samples in our laboratories. It demonstrated that the new method was robust and useful for monitoring and quantification of 7 tetracycline residues in food of animal origin.
This paper describes the matrix effect during the analysis of ten antibiotic compounds in water by SPE followed by HPLC-ESI-MS/MS. The target analytes were tetracycline, oxytetracycline (tetracyclines), sulfathiazole, sulfamethazine, sulfadiazine (sulfonamides), erythromycin-H(2) O, roxithromycine, spiramycin (macrolides), ofloxacin, and norfloxacin (quinolones). The matrix effect was examined for internal standards and the target analytes in five different water matrixes, with signal suppression being increased in the order: ultrapure water, tap water, river water, sewage effluent, and sewage influent. A combined application of the internal standards and matrix-matched extract calibration was shown to be successful in compensating the matrix effect for the analytes. The procedural recovery of the target compounds in sewage effluents and influents was higher than in river water samples, which was further enhanced by sample acidification to pH 2. The validity of the internal standard based matrix-matched calibration approach was verified by the standard addition method.
Tetracyclines have proven to be safe and effective antibiotics over decades but to date all approved members of the class have been discovered and manufactured by chemical modification of fermentation products, which greatly limits the number of new structures that can be explored as future medicines. This review summarizes research leading to the development of a platform synthetic technology that enabled the discovery of the clinical candidate eravacycline, as well as other promising new tetracycline antibiotics, and provides the basis for a practical route for their manufacture. The approach argues for a reassessment of other antibiotic classes based on natural products for which practical, fully synthetic routes have not yet been developed, suggesting that these may represent underdeveloped resources with great potential to offer safer and more effective anti-infective agents.
Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance.
This study investigated the treatment in the constructed Wuluo wetland, Taiwan, of 13 veterinary antibiotics, including five classes (tetracyclines, sulfonimides, chloramphenicol, fluoroquinolone, and dyes), five alkylphenolic compounds (nonylphenol di-ethoxylates [NP2EO], nonylphenol mono-ethoxylates [NP1EO], nonylphenol [NP], octylphenol [OP], and bisphenol A [BPA]), and three estrogens (17β-estradiol [E2], estriol [E3], and 17α-ethynylestradiol [EE2]). The veterinary antibiotics oxytetracycline (OTC), ciprofloxacin (CIP), chloramphenicol (CAP), oxolinic acid (OXO), sulfamonomethoxine (SMM), and sulfadimethoxine (SDM) were detected in 7.1-96.4% of samples with concentrations varying widely from not detected to 552 ng/L. Removal efficiencies within different units of the wetland system exceeded 87% for OTC, CAP, SMM, and SDM, excluding those for IP and OXO, which were 72.1% and 43%, respectively. The other seven antibiotics (tetracycline [TC], enrofloxacin [ENR], chlortetracycline [CTC], sulfamerazine [SMR], sulfamethazine [SMZ], malachite green [MG], and leucomalachite green [LMG]) were all below detection limits in all samples. Additionally, detection rates were as follows: NP1EO, 70.0%; NP2EO, 70.0%; 4-n-NP, 72.9%; 4-OP, 50.0%; BPA, 81.3%; E2, 52.1%; E3, 57.1%; and EE2, 31.3%. Concentrations of the alkylphenolic compounds were as follows: NP1EO, ND-1092.7; NP2EO, ND-643.7; 4-n-NP, ND-6812.3; 4-OP, ND-10400.1; and BPA, ND-1733 ng/L. Natural and synthetic estrogens E2, E3, and EE2 in samples were found in the ranges of ND-907.4, ND-749.5, and ND-226.0 ng/L, respectively. Analytical results show that with the exception of EE2 throughout the wetland system, target compounds were largely removed.
The chronic intermittent ethanol (CIE) paradigm is valuable for screening compounds for efficacy to reduce drinking traits related to alcohol use disorder (AUD), as it measures alcohol consumption and preference under physical dependence conditions. Air control-treated animals allow simultaneous testing of similarly treated, nondependent animals. As a consequence, we used CIE to test the hypothesis that tigecycline, a semisynthetic tetracycline similar to minocycline and doxycycline, would reduce alcohol consumption regardless of dependence status.
New pharmacotherapies to treat alcohol use disorders (AUD) are needed. Given the complex nature of AUD, there likely exist multiple novel drug targets. We, and others, have shown that the tetracycline drugs, minocycline and doxycycline, reduced ethanol (EtOH) drinking in mice. To test the hypothesis that suppression of high EtOH consumption is a general property of tetracyclines, we screened several derivatives for antidrinking activity using the Drinking-In-the-Dark (DID) paradigm. Active drugs were studied further using the dose-response relationship.