Tetracycline Antibiotics and Resistance Grossman, Trudy H
Cold Spring Harbor perspectives in medicine,
2016-Apr-01, 2016-04-00, 20160401, Letnik:
6, Številka:
4
Journal Article
Recenzirano
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Tetracyclines possess many properties considered ideal for antibiotic drugs, including activity against Gram-positive and -negative pathogens, proven clinical safety, acceptable tolerability, and the ...availability of intravenous (IV) and oral formulations for most members of the class. As with all antibiotic classes, the antimicrobial activities of tetracyclines are subject to both class-specific and intrinsic antibiotic-resistance mechanisms. Since the discovery of the first tetracyclines more than 60 years ago, ongoing optimization of the core scaffold has produced tetracyclines in clinical use and development that are capable of thwarting many of these resistance mechanisms. New chemistry approaches have enabled the creation of synthetic derivatives with improved in vitro potency and in vivo efficacy, ensuring that the full potential of the class can be explored for use against current and emerging multidrug-resistant (MDR) pathogens, including carbapenem-resistant Enterobacteriaceae, MDR Acinetobacter species, and Pseudomonas aeruginosa.
Antibiotics and corresponding resistance genes and resistant bacteria have been considered as emerging pollutants worldwide. Wastewater treatment plants (WWTPs) are potential reservoirs contributing ...to the evolution and spread of antibiotic resistance. In this study, total concentrations of tetracycline and sulfonamide antibiotics in final effluent were detected at 652.6 and 261.1ng/L, respectively, and in treated sludge, concentrations were at 1150.0 and 76.0μg/kg dry weight (dw), respectively. The quantities of antibiotic resistance genes and antibiotic resistant bacteria in final effluent were quantified in the range of 9.12×105–1.05×106 gene abundances /100mL (genomic copies/100mL) and 1.05×101–3.09×103CFU/mL, respectively. In treated sludge, they were quantified at concentrations of 1.00×108–1.78×109 gene abandances/100mL and 7.08×106–1.91×108CFU/100mL, respectively. Significant reductions (2–3 logs, p<0.05) of antibiotic resistance genes and antibiotic resistant bacteria were observed between raw influent and final effluent. The gene abundances of tetO and tetW normalized to that of 16S rRNA genes indicated an apparent decrease as compared to sulI genes, which remained stable along each treatment stage. Significant correlations (R2=0.75–0.83, p<0.05) between numbers of resistant bacteria and antibiotic concentrations were observed in raw influent and final effluent. No significance (R2=0.15, p>0.05) was found between tet genes (tetO and tetW) with concentration of tetracyclines identified in wastewater, while a significant correlation (R2=0.97, p<0.05) was observed for sulI gene and total concentration of sulfonamides. Correlations of the quantities of antibiotic resistance genes and antibiotic resistant bacteria with corresponding concentrations of antibiotics in sludge samples were found to be considerably weak (R2=0.003–0.07).
► Significant correlations were observed between tetracycline and sulfamethoxazole resistant bacteria and corresponding antibiotic concentrations in wastewater. ► A significant correlation was found between the copy number of sulI gene and total concentration of sulfonamides in wastewater. ► No significant correlations were observed between total tet genes (tetO and tetW) and total concentration of tetracyclines. ► Correlations of numbers of resistant genes and bacteria with corresponding concentrations of antibiotics in sludge samples were considerably weaker.
Tetracyclines have been one of the most successful classes of antibiotics. However, its extensive use has led to the emergence of widespread drug resistance, resulting in discontinuation of use ...against several bacterial infections. Prominent resistance mechanisms include drug efflux and the use of ribosome protection proteins. Infrequently, tetracyclines can be inactivated by the TetX class of enzymes, also referred to as tetracycline destructases. Low levels of tolerance to tetracycline in
and
have been previously attributed to the WhiB7-dependent TetV/Tap efflux pump. However,
is ∼500-fold more resistant to tetracycline than
and
In this report, we show that this high level of resistance to tetracycline and doxycycline in
is conferred by a WhiB7-independent tetracycline-inactivating monooxygenase, MabTetX (MAB_1496c). The presence of sublethal doses of tetracycline and doxycycline results in a >200-fold induction of MabTetX, and an isogenic deletion strain is highly sensitive to both antibiotics. Further, purified MabTetX can rapidly monooxygenate both antibiotics. We also demonstrate that expression of MabTetX is repressed by MabTetR
, by binding to an inverted repeat sequence upstream of MabTetR
; the presence of either antibiotic relieves this repression. Moreover, anhydrotetracycline (ATc) can effectively inhibit MabTetX activity
and decreases the MICs of both tetracycline and doxycycline
Finally, we show that tigecycline, a glycylcycline tetracycline, not only is a poor substrate of MabTetX but also is incapable of inducing the expression of MabTetX. This is therefore the first demonstration of a tetracycline-inactivating enzyme in mycobacteria. It (i) elucidates the mechanism of tetracycline resistance in
, (ii) demonstrates the use of an inhibitor that can potentially reclaim the use of tetracycline and doxycycline, and (iii) identifies two sequential bottlenecks-MabTetX and MabTetR
-for acquiring resistance to tigecycline, thereby reiterating its use against
.
► Inactivation of tetracycline-resistant Escherichia coli was compared to that of sensitive one. ► Tetracycline-resistant E. coli did not show any tolerance to UV lights. ► Tetracycline-resistant E. ...coli showed tolerance to chlorine of high dose. ► UV disinfection did not shift tetracycline-resistant E. coli more tolerant to tetracycline. ► Chlorination with a high dose shifted tetracycline-resistant E. coli more tolerant to tetracycline.
Antibiotic-resistant bacteria are an emerging threat to public health during drinking water consumption and reclaimed water reuse. Several studies have shown that the proportions of antibiotic-resistant bacteria in waters may increase when exposed to low doses of UV light or chlorine. In this study, inactivation of tetracycline-resistant Escherichia coli and antibiotic-sensitive E. coli by UV disinfection and chlorination was compared to determine the tolerance of tetracycline-resistant E. coli to UV light and chlorine, and tetracycline resistance of a tetracycline-resistant E. coli population was studied under different doses of the disinfectants. Our results showed that relative to antibiotic-sensitive E. coli, tetracycline-resistant E. coli had the same tolerance to UV light and a potentially higher tolerance to chlorination. The mortality frequency distributions of tetracycline-resistant E. coli exposed to tetracycline were shifted by both chlorination and UV disinfection. When compared to the hemi-inhibitory concentrations (IC50) of tetracycline-resistant E. coli with no exposure to UV or chlorination, the IC50 of tetracycline-resistant E. coli treated with tetracycline was 40% lower when inactivation by UV light or chlorination reached 3-log but was 1.18 times greater when inactivation by chlorination reached 4.3-log. Chlorination applied to drinking water or reclaimed water treatment may increase the risk of selection for highly tetracycline-resistant E. coli.
Although tetracyclines are an important class of antibiotics for use in agriculture and the clinic, their efficacy is threatened by increasing resistance. Resistance to tetracyclines can occur ...through efflux, ribosomal protection, or enzymatic inactivation. Surprisingly, tetracycline enzymatic inactivation has remained largely unexplored, despite providing the distinct advantage of antibiotic clearance. The tetracycline destructases are a recently discovered family of tetracycline-inactivating flavoenzymes from pathogens and soil metagenomes that have a high potential for broad dissemination. Here, we show that tetracycline destructases accommodate tetracycline-class antibiotics in diverse and novel orientations for catalysis, and antibiotic binding drives unprecedented structural dynamics facilitating tetracycline inactivation. We identify a key inhibitor binding mode that locks the flavin adenine dinucleotide cofactor in an inactive state, functionally rescuing tetracycline activity. Our results reveal the potential of a new tetracycline and tetracycline destructase inhibitor combination therapy strategy to overcome resistance by enzymatic inactivation and restore the use of an important class of antibiotics.
Tetracyclines (TCs) are a group of broad-spectrum antibiotics having vast human, veterinary, and aquaculture applications. The continuous release of TCs residues into the environment and the ...inadequate removal through the conventional treatment systems result in its prevalent occurrence in soil, surface water, groundwater, and even in drinking water. As aqueous TCs contamination is the tip of the iceberg, and TCs possess good sorption capacity towards soil, sediments, sludge, and manure, it is insufficient to rely on the sorptive removal in the conventional water treatment plants. The severity of the TCs contamination is evident from the emergence of TCs resistance in a wide variety of microorganisms. This paper reviews the recent research on the TCs occurrence in the environmental matrices, fate in natural systems, toxic effects, and the removal methods. The high performance liquid chromatography (HPLC) determination of TCs in environmental samples and the associated technology developments are analyzed. The benefits and limitations of biochemical and physicochemical removal processes are also discussed. This work draws attention to the inevitability of proper TC sludge management. This paper also gives insight into the limitations of TCs related research and the future scope of research in environmental contamination by TCs residues.
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•Fate and transport of tetracyclines (TCs) in environmental matrices are explained.•Qualitative and quantitative determination of TCs is outlined.•Toxic effects of TCs in microbes, plants, and animals are summarized.•Major technologies reported for TCs removal are discussed in detail.
Graphitic carbon nitride is considered as one of the promising photocatalysts for pollution elimination from wastewater. Manipulating the microstructure of carbon nitride remains a challengeable ...task, which is essential for improving light absorption, separating photogenerated carrier and creating reactive sites. Herein, a carbon vacancy modified hierarchical carbon nitride microrod (CN1.5) has been prepared templated from a melamine-NH2OH·HCl complex. The hierarchical microrods are demonstrated to be comprised of interconnected nanosheets with rich carbon vacancies, which endows it with high specific surface area, enhanced light utilization efficiency, available reactive sites, improved charge carrier separation and numerous mass-transport channels. The resultant photocatalyst CN1.5 exhibits an excellent photodegradation efficiency of 87.9% towards tetracycline under visible light irradiation. The remarkable apparent rate constant of 4.91 × 10−2 min−1 is 7.3 times higher than that of bulk CN. In addition, the degradation pathways are deduced base on the observation of degradation intermediates generating in the photocatalytic process. Mechanism investigation indicates that the major contribution for photodegradation is attributed to ·O2–, 1O2 and H2O2 species. This work provides new insights into advancing carbon nitride's microstructure to improve photocatalytic degradation performance for highly efficient antibiotic removal and environment remediation.
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•A melamine complex was constructed with a well-defined structure to synthesize carbon nitride.•CN1.5 exhibits a hierarchical microrod morphology derived from a bubble template.•Carbon vacancies were implanted into the hierarchical structure working as active sites.•CN1.5 shows a high photocatalytic degradation efficiency towards TC under visible light.•·O2–, 1O2 and H2O2 are main reactive oxygen species contributing to TC photodegradation.
Tigecycline is used in multidrug regimens for salvage therapy of
infections but is often poorly tolerated and has no oral formulation. Here, we report similar
activity of two newly approved ...tetracycline analogs, omadacycline and eravacycline, against 28 drug-resistant clinical isolates of
complex. Since omadacycline and eravacycline appear to be better tolerated than tigecycline and since omadacycline is also formulated for oral dosing, these tetracycline analogs may represent new treatment options for
infections.
Manure application contributes to the increased environmental burden of antibiotic resistance genes (ARGs). We investigated the response of tetracycline (tet) resistance genes and bacterial taxa to ...manure application amended with tetracyclines over two months. Representative tetracyclines (oxytetracycline, chlorotetracycline and doxycycline), tet resistance genes (tet(M), tet(O), tet(W), tet(S), tet(Q) and tet(X)) and bacterial taxa in the untreated soil, +manure, and +manure+tetracyclines groups were analyzed. The abundances of all tet resistance genes in the +manure group were significantly higher than those in the untreated soil group on day 1. The abundances of all tet resistance genes (except tet(Q) and tet(X)) were significantly lower in the +manure group than those in the +manure+tetracyclines group on day 30 and 60. The dissipation rates were higher in the +manure group than those in the +manure+tetracyclines group. Disturbance of soil bacterial community composition imposed by tetracyclines was also observed. The results indicated that tetracyclines slowed down the dissipation of tet resistance genes in arable soil after manure application. Application of manure amended with tetracyclines may provide a significant selective advantage for species affiliated to the taxonomical families of Micromonosporaceae, Propionibacteriaceae, Streptomycetaceae, Nitrospiraceae and Clostridiaceae.
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•Abundances of most tet genes significantly increased after manure application.•Significantly high abundance of tet RPP genes lasted more than two months.•Dissipation rates of tet genes were largely depended on the initial abundances.•TCs slowed down the dissipation of tet resistance genes after manure application.•TCs amendment provided a significantly selective advantage for some families.
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•A novel adsorbent contained amino groups and coordinated Fe(III) was prepared.•The adsorbent had high adsorption efficiency for both TC and Cu(II).•The synergistic effects of TC and ...Cu(II) on the adsorption were found.•TC–Cu(II) complex act as a bridge between adsorbates and adsorbent.•Fe(III) and amino groups were complexed with amide of TC and Cu(II), respectively.
Finding effective methods for simultaneous removal of antibiotics and heavy metals has attracted increasing concern since both of them are frequently detected in aquatic environments. In this study, a novel mesoporous silica adsorbent (Fe-N,N-SBA15) contained dual-functional groups was synthesized by first grafting di-amino groups on SBA15, and then coordinating Fe(III) onto the adsorbent. The adsorbent was then used in the synchronous elimination of tetracycline (TC) and Cu(II) from water, which was deeply studied by solution pH, kinetics, equilibriums in sole and binary systems. It was found that the adsorbent had high affinity for both TC and Cu(II) and synergistic effects on the adsorption were found. The solution pH remarkably affected the adsorption due to pH-dependent speciation of TC, Cu(II), TC–Cu(II) complex and the surface properties of the adsorbent. Increasing adsorption amount of TC and Cu(II) on the adsorbent could be attributed to the formation of complex TC–Cu(II) bridging or the stronger affinity of the adsorbent for the TC–Cu(II) complex than that for TC or Cu(II) separately. FT-IR and XPS studies revealed that Fe(III) and amino groups on the adsorbent were complexed with the amide of TC and Cu(II), respectively. The recyclabilities of the adsorbent were also evaluated and the Fe-N,N-SBA15 exhibited good reusability for TC and Cu(II) removal. This study shows guidelines and offers an innovative, effective method for the synergistic removal of antibiotics and heavy metals from aquatic environments.
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