Tetracycline (INN) is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein synthesis inhibitor. It is commonly used to treat acne today, and, more recently, rosacea, and is historically important in reducing the number of deaths from cholera. Tetracycline is marketed under the brand names Sumycin, Tetracyn, and Panmycin, among others. Actisite is a thread-like fiber formulation used in dental applications. It is also used to produce several semisynthetic derivatives, which together are known as the tetracycline antibiotics. The term "tetracycline" is also used to denote the four-ring system of this compound; "tetracyclines" are related substances that contain the same four-ring system.
Antigen Description
The tetracycline and BSA (bovine serum albumin) (10 mg each) are conjugated by EDC method in 0.1 M MES pH 5.0. The amine group in the tetracycline is directly linked to a carboxyl group in the KLH without any linker by EDC conjugation method. Given the molecular weights of tetracycline hydrochloride and BSA are 480.9 Da and 66.4 kDa, respectively, and the molar ratio of tetracycline:BSA in the conjugation solution is 138:1. The resultant conjugation solution is then buffer-exchanged with 20 mM PBS, pH 7.4. The number of tetracycline that is actually conjugated to each BSA molecule is not determined.
Keywords
Tetracycline
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Background
Originally isolated from Streptomyces spp, tetracyclines are an important class of broad-spectrum antibiotics that prevent bacterial growth by inhibiting protein biosynthesis and can be used for both gram-positive and gram-negative bacterial infections as well as infections caused by protozoan parasites and intracellular organisms. Four linearly condensed benzene rings in a hydronaphtacene nucleus make up the basic structure of tetracyclines, and the essential difference between analogs in this class is the difference in the C5, C6, C7, and C9 substituents.
Figure 1. Tetracyclines—the general chemical structure and conventional numbering of the condensed rings and key positions (Source: Rusu A, et al. 2021)
Tetracycline inhibits the synthesis of bacterial protein by binding to bacterial ribosomes and interacting with highly conserved 16S ribosomal RNA (rRNA) in the 30S ribosomal subunit. Tetracyclines are recommended for first-line treatment of many indications, including skin infections, bone and joint infections, sexually transmitted infections. However, with the emergence of antibiotic resistance, the clinical effectiveness of tetracyclines has declined. In the early days most commensal bacteria and pathogenic bacteria were susceptible to tetracyclines, while later it was found that Staphylococcus aureus and Streptococcus pyogenes developed resistance. First- and second-generation tetracyclines have shown improved activity against Staphylococcus aureus, but many Streptococcus species remain resistant. The rate of acquired resistance to tetracyclines has increased over time, leading to their use primarily as second-line therapeutic agents of choice. The most common mechanisms of acquired resistance are the efflux pump and ribosomal protective proteins. The efflux pump is an anti-transporter that actively pumps antibiotics out of the bacterial cell. Ribosome-protective proteins protect ribosomes from the inhibitory effects of tetracyclines, probably because these proteins cause conformational changes in the ribosome structure that prevent tetracycline binding or lead to its dissociation.
The first generation of tetracyclines were obtained from biosynthesis, the second generation of drugs were semi-synthetic products, and the third generation of drugs were completely synthesized, resulting in side chains that were more complex than those of the previous generations, which enhanced antimicrobial activity. In order to overcome the major resistance mechanism of tetracyclines, researchers designed a third generation of tetracyclines by adding a lipophilic side group at the C9 position of the D-ring, which further enhances the activity of the antibiotic.
Figure 2. Chemical structures of tetracyclines (Source: LaPlante KL, et al. 2022)
References
1. Rusu A, et al. The Development of Third-Generation Tetracycline Antibiotics and New Perspectives. Pharmaceutics. 2021 Dec 5;13(12):2085
2. LaPlante KL, et al. Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance. Ann Med. 2022 Dec;54(1):1686-1700.
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References
Critical insight into the fate of antibiotic resistance genes during biological treatment of typical biowastes
Antibiotic resistance genes (ARGs) in biowaste, such as livestock manure and excess activated sludge, pose potential threat to human and ecological health when applied to agricultural fields. Biological treatment approaches, such as thermophilic composting/vermicomposting and anaerobic digestion, widely adopted to stabilize biowaste have demonstrated significant effects on the fate of ARGs. However, the influence of these biological treatments on ARGs is not known. This review summarizes the occurrence of ARGs in biowaste and the impact of thermophilic composting, vermicomposting, and anaerobic digestion on the fate of ARGs with discussion on factors, including substrate properties, pretreatments, additives, and operational parameters, associated with ARGs during biological treatment of biowaste. Finally, this review explores the research implications and proposes new avenues in the field of biological treatment of organic waste.
Low-dose effects on thyroid disruption in zebrafish by long-term exposure to oxytetracycline
As a feed additive in agriculture, the antibiotic oxytetracycline (OTC) has become widely distributed in the natural environment, leading to the exposure of many organisms to low doses of OTC. Although OTC is clinically contraindicated in children because of its multiple side effects, the effect of exposure to low doses of environmental OTC on children is unknown, particularly during development. In this study, we investigated the effects of OTC on the thyroid endocrine system in zebrafish, through determinations of the whole-body contents of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) by enzyme-linked immunosorbent assay, and analysis of the mRNA expression of regulatory genes involved in the hypothalamus-pituitary-thyroid (HPT) axis using quantitative real-time polymerase chain reaction. Zebrafish embryos were exposed to OTC at environmentally relevant concentrations from 2 h to 120 days post-fertilisation. After exposure to OTC at 1,000 and 5,000 ng/L, T3 contents were significantly enhanced (37.8% and 45.1%, respectively) and TSH contents were reduced (16% and 16.3%, respectively) compared with those in the controls. The OTC-driven increase in the transcription of genes involved in thyroid synthesis (tpo and nis) may be responsible for the altered T3 levels. These data indicate that OTC may cause thyroid dysfunction and lead to reduced TSH secretion owing to enhanced negative feedback control of the HPT axis. Meanwhile, a decrease in body length, weight, and BMI and an increase in heart rate were observed with increasing OTC exposure. In conclusion, our results indicate that long-term exposure to low concentrations of OTC may alter the transcription of key genes involved in the HPT axis, as well as T3 and TSH contents, thereby disrupting the thyroid system and affecting the growth and development of zebrafish.
COA![Tetracycline [BSA]](https://resource.creative-diagnostics.com/diagnostics/productimages-1/Tetracycline [BSA].jpg)
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Figure 1. Tetracyclines—the general chemical structure and conventional numbering of the condensed rings and key positions
Figure 2. Chemical structures of tetracyclines
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