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1.
Water Res ; 196: 117003, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33730544

RESUMEN

In this study, we evaluated the biotransformation mechanisms of lincomycin (LIN) and three fluoroquinolone antibiotics (FQs), ciprofloxacin (CFX), norfloxacin (NFX), and ofloxacin (OFX), which regularly enter aquatic environments through human activities, by different ammonia-oxidizing microorganisms (AOM). The organisms included a pure culture of the complete ammonia oxidizer (comammox) Nitrospira inopinata, an ammonia oxidizing archaeon (AOA) Nitrososphaera gargensis, and an ammonia-oxidizing bacterium (AOB) Nitrosomonas nitrosa Nm90. The removal of these antibiotics by the pure microbial cultures and the protein-normalized biotransformation rate constants indicated that LIN was significantly co-metabolically biotransformed by AOA and comammox, but not by AOB. CFX and NFX were significantly co-metabolized by AOA and AOB, but not by comammox. None of the tested cultures transformed OFX effectively. Generally, AOA showed the best biotransformation capability for LIN and FQs, followed by comammox and AOB. The transformation products and their related biotransformation mechanisms were also elucidated. i) The AOA performed hydroxylation, S-oxidation, and demethylation of LIN, as well as nitrosation and cleavage of the piperazine moiety of CFX and NFX; ii) the AOB utilized nitrosation to biotransform CFX and NFX; and iii) the comammox carried out hydroxylation, demethylation, and demethylthioation of LIN. Hydroxylamine, an intermediate of ammonia oxidation, chemically reacted with LIN and the selected FQs, with removals exceeding 90%. Collectively, these findings provide important fundamental insights into the roles of different ammonia oxidizers and their intermediates on LIN and FQ biotransformation in nitrifying environments including wastewater treatment systems.


Asunto(s)
Amoníaco , Nitrificación , Antibacterianos , Archaea , Biotransformación , Fluoroquinolonas , Humanos , Lincomicina , Nitrosomonas , Oxidación-Reducción , Filogenia , Microbiología del Suelo
2.
Bioresour Technol ; 329: 124913, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33711716

RESUMEN

This study investigated the tolerance, defensive response and methanogenic pathways of anaerobic granular slugde and anaerobic suspended sludge (AGS and ASS) exposed to different LCM concentrations. AGS presented a higher tolerance to LCM stress, accompanied with 20.8 ± 2.6% enhancement in methane production at 1000 mg/L LCM, which was likely attributed to the less cell deaths and extracellular polymeric substances (EPSs) protection. In the acidification stage, acetate accumulation was stimulated and the activity of acetate kinase was promoted by LCM. In the methanogenesis stage, propionate and butyrate utilization for methane production were impaired after LCM addition. LCM also improved the activity of pyruvate-ferredoxin oxidoreductase and strengthened the process of hydrogenotrophic methanogenesis, likely by accelerating interspecies electron transfer mediated by hydrogen. ErmB and ermF were the dominate LCM resistance genes in AGS under LCM pressure conferring the resistance mechanism of ribosomal protection.


Asunto(s)
Biocombustibles , Aguas del Alcantarillado , Anaerobiosis , Reactores Biológicos , Lincomicina , Metano
3.
Carbohydr Polym ; 261: 117875, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33766362

RESUMEN

Hydrogels are three-dimensional polymeric networks capable of absorbing large amounts of water or biological fluids with the properties resembling natural living tissues. Herein, polyvinyl alcohol (PVA)/N-succinyl chitosan (NSCS)/lincomycin hydrogels for wound dressing were prepared by the freezing/thawing method, then characterized by FTIR, SEM, and TGA. The compression strength, swelling behavior, water retention capacity, antibacterial activity, drug release and cytotoxicity were systematically investigated. The results showed that the introduction of NSCS remarkably enhanced the swelling capacity, leading to the maximum swelling ratio of 19.68 g/g in deionized water. The optimal compression strength of 0.75 MPa was achieved with 30 % NSCS content.Additionally, the incorporation of lincomycin brought a remarkable antibacterial activity against both Escherichia coli and Staphylococcus aureus. Specifically, 77.71 % of Staphylococcus aureus was inhibited with 75 µg/mL lincomycin, while the MTT assay demonstrated the nontoxic nature of the composite hydrogels. In summary, this PVA/NSCS/lincomycin hydrogel showed promising potential for wound dressing.


Asunto(s)
Vendas Hidrocoloidales , Quitosano/química , Lincomicina/administración & dosificación , Alcohol Polivinílico/química , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Supervivencia Celular/efectos de los fármacos , Quitosano/síntesis química , Quitosano/farmacología , Liberación de Fármacos , Humanos , Lincomicina/química , Lincomicina/farmacocinética , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Alcohol Polivinílico/síntesis química , Alcohol Polivinílico/farmacología
4.
Ecotoxicol Environ Saf ; 209: 111802, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33360784

RESUMEN

As the antibiotic pollution source in the environment, a large amount of biowastes generated from antibiotic fermentation manufacture needs proper disposal. Recycling the biowaste as resources and nutrients is of great interest. Besides, degradation or removal of antibiotics is indispensable for the reclamation of antibiotic manufacturing biowaste. To establish environmentally friendly disposal strategies for lincomycin manufacturing biowaste (LMB), we screened the microbial strains that could efficiently degrade lincomycin from the antibiotic wastewater treatment plant. Among them, three novel strains were identified as Bacillus subtilis (strain LMB-A), Rhodotorula mucilaginosa (strain LMB-D) and Penicillium oxalicum (strain LMB-E), respectively. LMB-A and LMB-D could degrade 92.69% and 74.05% of lincomycin with an initial concentration of 1117.55 mg/L in 144 h, respectively. The lincomycin degradation products were formed by the breakage of amide bond or losing N-demethyl/thiomethyl group from the pyrrolidine/pyranose ringcata cata catalyzed by the strains. Moreover, LMB-A could decontaminate LMB, and the decontaminated LMB could be used as a nitrogen source to culture salt-resistant bacteria and other useful microorganisms. LMB-A and LMB-D have the potential to be used for the bioremediation of water and soil polluted by lincomycin and its analogs. LMB-E could degrade 88.20% LMB after 144-h cultivation. In summary, this study gives an insight into the green disposal of LMB, and the established strategy has potential application for biotreatment of other antibiotic fermentation manufacturing biowastes.


Asunto(s)
Antibacterianos/metabolismo , Biodegradación Ambiental , Lincomicina/metabolismo , Bacterias/metabolismo , Fermentación , Penicillium/metabolismo , Rhodotorula , Suelo
5.
J Environ Qual ; 49(1): 236-245, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33016366

RESUMEN

Antimicrobials used in livestock production can be present in manure via excretion in the feces and/or urine. Application of raw or processed (composted or stockpiled) manure to crop and pasture land as a plant nutrient source can result in antimicrobial transport to surface waters via rainfall or snowmelt runoff. Little is known regarding antimicrobial persistence in aquatic ecosystems. Consequently, dissipation of environmentally relevant concentrations of three veterinary antimicrobials (lincomycin, chlortetracycline, and sulfamethazine) was studied in three wetlands on the Canadian Prairies. Study wetlands were fortified in the fall to simulate antimicrobial transport via rainfall runoff from fall manure applications to the wetland catchments. After fortification, water column concentrations of all three antimicrobials decreased through September and October. Plotting natural logarithm values of antimicrobial concentration against time resulted in linear relationships for all three antimicrobials, indicating that the summation of all dissipation processes for each antimicrobial could be described by first-order kinetics. The slopes of the three plots were significantly different, indicating that the order of dissipation was lincomycin < sulfamethazine < chlortetracycline. Consequently, the dissipation DT50 (time required for 50% antimicrobial dissipation) values for lincomycin (14.0 d), sulfamethazine (7.0 d), and chlortetracycline (3.3 d) were significantly different. The longer DT50 values of lincomycin and sulfamethazine suggest that environmentally relevant concentrations of these antimicrobials may affect bacterial production in prairie wetlands.


Asunto(s)
Antiinfecciosos , Clortetraciclina , Canadá , Ecosistema , Pradera , Lincomicina , Sulfametazina , Humedales
6.
Food Chem ; 333: 127477, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-32673956

RESUMEN

As a veterinary antibiotic, lincomycin (LIN) residues in milk are raising concerns of public on account of potential harm to human health. Efficient strategy is eagerly desired for detection of LIN from milk samples. Hence, lincomycin molecularly imprinted membranes (LINMIMs) were developed for selective separation of LIN as an efficient pretreatment of milk samples. The synergistic effect of polyethylenimine and dopamine provided effective antifouling performance by improving the hydrophilicity. Based on click chemistry, specific recognition sites were facilely formed on membranes using 4-vinylpyridine as functional monomers. The satisfactory rebinding capacity (151.62 mg g-1), permselectivity (4.43), together with the linear dependence (R2 = 0.9902) of concentrations in eluents and original samples. Moreover, the method was utilized to determine LIN from milk, with good recovery and relative standard deviation. Achievements in this work will actively promote the development of efficient detection technology.


Asunto(s)
Incrustaciones Biológicas/prevención & control , Contaminación de Alimentos/análisis , Lincomicina/análisis , Lincomicina/aislamiento & purificación , Membranas Artificiales , Leche/química , Impresión Molecular , Animales , Residuos de Medicamentos/análisis , Residuos de Medicamentos/aislamiento & purificación
7.
J Popul Ther Clin Pharmacol ; 27(S Pt 1): e5-e10, 2020 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-32543164

RESUMEN

The COVID-19 virus has spread rapidly around the world and there are many patients in multiple countries. Great efforts have been made to find effective medications against the COVID-19. This study aims to compare the effectiveness of LINCOCIN® and AZITRO® in the treatment of COVID-19 associated pneumonia. A total of 24 hospitalized patients aged between 30-80 years who were admitted to the Tarsus Medical Park Hospital between February to March 2020 was included in the study. The patients were divided into LINCOCIN® and AZITRO® treatment groups. Bronchoalveolar-lavage PCR results were compared after treatment. The mean age was 58.4±15.4 years in the LINCOCIN® group and 59.1±16.6 years in the AZITRO® group. In the LINCOCIN® group, the rate of males was 66.7% and it was 58.3% in the AZITRO® group. There were no statistical differences in terms of age and gender between the groups. On the 6th day after starting treatment, negative bronchoalveolar PCR result was 83.3% in the LINCOCIN® group and 33.3% in the AZITRO® group. The negative bronchoalveolar PCR proportion was significantly higher in the LINCOCIN® group than in the AZITRO® group. LINCOCIN® usage may be more appropriate in the treatment of COVID-19 associated pneumonia. Further studies with a large sample size should clarify these results.


Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Infecciones por Coronavirus/complicaciones , Lincomicina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , Betacoronavirus , Líquido del Lavado Bronquioalveolar/virología , Femenino , Humanos , Lincomicina/administración & dosificación , Lincomicina/efectos adversos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/etiología , Neumonía Viral/virología , Estudios Prospectivos , Factores de Riesgo
8.
Ecotoxicol Environ Saf ; 201: 110725, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32474209

RESUMEN

Lincomycin hydrochloride is one of the commonly used drugs in clinic. However, it has many side effects on patients, and its mechanism is still poorly understood. In this study, 6 h post-fertilization (6 hpf) zebrafish embryos were exposed to several concentrations of lincomycin hydrochloride (15, 30, 60 µg/mL) for up to 24 or 96 hpf to detect their developmental toxicity and neurotoxicity, and to 6 days post-fertilization (6 dpf) to detect their behavioral toxicity. Our results showed that lincomycin hydrochloride could lead to embryonic head deformities (unclear ventricles, smaller ventricles, fewer new neurons). The studies showed that the frequency of spontaneous tail flick of zebrafish embryo increased at 24 hpf, and the lincomycin hydrochloride exposed zebrafish embryos showed increased heart rate, shorter body length, and yolk sac edema with severe pericardial edema at 96 hpf. The studies also showed that lincomycin hydrochloride increased oxidative stress level, Acetylcholinesterase (AChE) activity, ATPase activity and apoptosis in zebrafish larvae. In addition, the swimming behavior of zebrafish larvae decreased with the increase of lincomycin hydrochloride concentration, but the angular velocity and meandering degree increased, which might be due to the decreased activity of AChE and ATPase, as well as the decreased expression of genes related to neurodevelopment and neurotransmitter system, leading to the change of their motor behaviors. In summary, we found that lincomycin hydrochloride induced developmental toxicity and neurotoxicity in zebrafish larvae, contributing to a more comprehensive evaluation of the safety of the drug.


Asunto(s)
Lincomicina/toxicidad , Síndromes de Neurotoxicidad/etiología , Acetilcolinesterasa/metabolismo , Adenosina Trifosfatasas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Desarrollo Embrionario/efectos de los fármacos , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Síndromes de Neurotoxicidad/congénito , Estrés Oxidativo/efectos de los fármacos , Pez Cebra
9.
Brasília; s.n; 17 jun. 2020.
No convencional en Portugués | LILACS, BRISA/RedTESA, PIE | ID: biblio-1100423

RESUMEN

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos.


Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Betacoronavirus/efectos de los fármacos , Evaluación de la Tecnología Biomédica , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Heparina/uso terapéutico , Lincomicina/uso terapéutico , Azitromicina/uso terapéutico , Ritonavir/uso terapéutico , Bloqueadores del Receptor Tipo 2 de Angiotensina II/uso terapéutico , Lopinavir/uso terapéutico , Interferón beta-1a/uso terapéutico , Interferon beta-1b/uso terapéutico , Interferón alfa-2/uso terapéutico , Hidroxicloroquina/uso terapéutico , Medicina China Tradicional , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Óxido Nítrico/uso terapéutico
10.
Food Chem ; 318: 126510, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32155562

RESUMEN

This study is devoted to the development of a sensitive immunochromatographic analysis (ICA) for simultaneous determination of tylosin (TYL) and lincomycin (LIN) as antibiotics of the macrolide and lincosamide classes, widely used in animal husbandry and implicated in the contamination of foodstuffs. The ICA was implemented in an indirect competitive format, using antispecies antibodies conjugated with gold nanoparticles (GNPs) as a label. After the multistep optimization, the developed double ICA allowed for antibiotics detection with instrumental limits of detection/cutoff levels of 0.09/2 ng/mL and 0.008/0.8 ng/mL for TYL and LIN, respectively, within 10 min. The cross-reactivity was 40% to lincosamide clindamycin and negligible to other antibiotics tested. The test system allowed for the detection of TYL and LIN in milk, honey, and eggs. The recoveries of antibiotics from foodstuffs were 87.5-112.5%. The results demonstrate that the developed double ICA is an effective approach for the detection of other food contaminants.


Asunto(s)
Antibacterianos/análisis , Cromatografía de Afinidad/métodos , Contaminación de Alimentos/análisis , Lincomicina/análisis , Tilosina/análisis , Animales , Huevos/análisis , Análisis de los Alimentos/métodos , Oro/análisis , Miel/análisis , Nanopartículas del Metal/química , Leche/química , Sensibilidad y Especificidad
11.
Artículo en Inglés | MEDLINE | ID: mdl-32086145

RESUMEN

The aim of this study was to develop a rapid and sensitive immunochromatographic test system for the detection of lincomycin (LIN), which belongs to the lincosamide group of antibiotics and contaminates food products of animal origin. Two formats of immunochromatographic analysis (ICA) based on different approaches of introducing gold nanoparticles (GNPs) as a label were compared. It was demonstrated that an indirect ICA method where GNPs were conjugated with anti-species antibodies allowed the achievement of both instrumental and visual detection limits of LIN almost two orders of magnitude lower than those achieved in the standard direct ICA format. In the optimized conditions, the developed indirect ICA allowed for the detection of LIN within 15 min, with instrumental and visual detection limits of 8 pg/mL and 0.8 ng/mL. The assay showed 40% cross-reactivity to clindamycin (CLIN) as a structural analogue of LIN, with no interaction with antibiotics from other classes. The developed ICA was applied for LIN detection in a panel of food products. No treatment of cow milk was necessary before the analysis. For chicken eggs and honey, a simple procedure of preliminary sample preparation was developed, which fully prevented a matrix influence on the assay results. It was demonstrated that ICA could detect LIN in food products while preserving the same analytical characteristics as in the buffer. The analytical recoveries of LIN in foodstuffs were 93.8-125% with coefficients of variations of 5.3-14.0%.


Asunto(s)
Cromatografía de Afinidad/métodos , Residuos de Medicamentos/análisis , Lincomicina/análisis , Animales , Bovinos , Residuos de Medicamentos/aislamiento & purificación , Límite de Detección , Lincomicina/aislamiento & purificación , Leche/química
12.
Microb Cell Fact ; 19(1): 30, 2020 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-32050973

RESUMEN

BACKGROUND: Lincomycin, produced by Streptomyces lincolnensis, is a lincosamide antibiotic and widely used for the treatment of the infective diseases caused by Gram-positive bacteria. The mechanisms of lincomycin biosynthesis have been deeply explored in recent years. However, the regulatory effects of LmbU that is a transcriptional regulator in lincomycin biosynthetic (lmb) gene cluster have not been fully addressed. RESULTS: LmbU was used to search for homologous LmbU (LmbU-like) proteins in the genomes of actinobacteria, and the results showed that LmbU-like proteins are highly distributed regulators in the biosynthetic gene clusters (BGCs) of secondary metabolites or/and out of the BGCs in actinomycetes. The overexpression, inactivation and complementation of the lmbU gene indicated that LmbU positively controls lincomycin biosynthesis in S. lincolnensis. Comparative transcriptomic analysis further revealed that LmbU activates the 28 lmb genes at whole lmb cluster manner. Furthermore, LmbU represses the transcription of the non-lmb gene hpdA in the biosynthesis of L-tyrosine, the precursor of lincomycin. LmbU up-regulates nineteen non-lmb genes, which would be involved in multi-drug flux to self-resistance, nitrate and sugar transmembrane transport and utilization, and redox metabolisms. CONCLUSIONS: LmbU is a significant pleiotropic transcriptional regulator in lincomycin biosynthesis by entirely activating the lmb cluster and regulating the non-lmb genes in Streptomyces lincolnensis. Our results first revealed the pleiotropic regulatory function of LmbU, and shed new light on the transcriptional effects of LmbU-like family proteins on antibiotic biosynthesis in actinomycetes.


Asunto(s)
Regulación Bacteriana de la Expresión Génica/genética , Lincomicina/biosíntesis , Streptomyces , Factores de Transcripción/genética , Transcriptoma/genética , Proteínas Bacterianas/genética , Perfilación de la Expresión Génica/métodos , Pleiotropía Genética/genética , Familia de Multigenes/genética , Metabolismo Secundario/genética , Streptomyces/genética , Streptomyces/metabolismo
13.
Appl Microbiol Biotechnol ; 104(6): 2575-2587, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31993701

RESUMEN

Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in Streptomyces lincolnensis, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (lmbA and lmbV), three resistance genes (lmrA, lmrB and lmrC), and a regulatory gene (lmbU) within the lincomycin biosynthetic gene (lin) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene SLCG_3127 encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of SLCG_3127 and SLCG_Lrp was precisely identified. Inactivation of SLCG_3127 in S. lincolnensis resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside lin cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation.


Asunto(s)
Proteínas Bacterianas/genética , Regulación Bacteriana de la Expresión Génica , Proteína Reguladora de Respuesta a la Leucina/genética , Lincomicina/biosíntesis , Streptomyces/genética , Transcripción Genética , Vías Biosintéticas , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Familia de Multigenes , Factores de Transcripción/genética
14.
J Am Chem Soc ; 142(7): 3440-3448, 2020 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-31944685

RESUMEN

Antitumor pyrrolobenzodiazepines (PBDs), lincosamide antibiotics, quorum-sensing molecule hormaomycin, and antimicrobial griselimycin are structurally and functionally diverse groups of actinobacterial metabolites. The common feature of these compounds is the incorporation of l-tyrosine- or l-leucine-derived 4-alkyl-l-proline derivatives (APDs) in their structures. Here, we report that the last reaction in the biosynthetic pathway of APDs, catalyzed by F420H2-dependent Apd6 reductases, contributes to the structural diversity of APD precursors. Specifically, the heterologous overproduction of six Apd6 enzymes demonstrated that Apd6 from the biosynthesis of PBDs and hormaomycin can reduce only an endocyclic imine double bond, whereas Apd6 LmbY and partially GriH from the biosyntheses of lincomycin and griselimycin, respectively, also reduce the more inert exocyclic double bond of the same 4-substituted Δ1-pyrroline-2-carboxylic acid substrate, making LmbY and GriH unusual, if not unique, among reductases. Furthermore, the differences in the reaction specificity of the Apd6 reductases determine the formation of the fully saturated APD moiety of lincomycin versus the unsaturated APD moiety of PBDs, providing molecules with optimal shapes to bind their distinct biological targets. Moreover, the Apd6 reductases establish the first F420H2-dependent enzymes from the luciferase-like hydride transferase protein superfamily in the biosynthesis of bioactive molecules. Finally, our bioinformatics analysis demonstrates that Apd6 and their homologues, widely distributed within several bacterial phyla, play a role in the formation of novel yet unknown natural products with incorporated l-proline-like precursors and likely in the microbial central metabolism.


Asunto(s)
Benzodiazepinas/metabolismo , Lincomicina/biosíntesis , Oxidorreductasas/metabolismo , Pirroles/metabolismo , Benzodiazepinas/química , Benzodiazepinas/farmacología , Catálisis , Depsipéptidos/biosíntesis , Depsipéptidos/química , Depsipéptidos/farmacología , Lincomicina/química , Lincomicina/farmacología , Modelos Moleculares , Oxidorreductasas/química , Péptidos Cíclicos/biosíntesis , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Prolina/análogos & derivados , Prolina/metabolismo , Pirroles/química , Pirroles/farmacología , Riboflavina/análogos & derivados , Riboflavina/química , Riboflavina/metabolismo , Especificidad por Sustrato , Tirosina/análogos & derivados , Tirosina/metabolismo
15.
Plant J ; 101(1): 156-170, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31498930

RESUMEN

Lincomycin (LIN)-mediated inhibition of protein synthesis in chloroplasts prevents the greening of seedlings, represses the activity of photosynthesis-related genes in the nucleus, including LHCB1.2, and induces the phenylpropanoid pathway, resulting in the production of anthocyanins. In genomes uncoupled (gun) mutants, LHCB1.2 expression is maintained in the presence of LIN or other inhibitors of early chloroplast development. In a screen using concentrations of LIN lower than those employed to isolate gun mutants, we have identified happy on lincomycin (holi) mutants. Several holi mutants show an increased tolerance to LIN, exhibiting de-repressed LHCB1.2 expression and chlorophyll synthesis in seedlings. The mutations responsible were identified by whole-genome single-nucleotide polymorphism (SNP) mapping, and most were found to affect the phenylpropanoid pathway; however, LHCB1.2 expression does not appear to be directly regulated by phenylpropanoids, as indicated by the metabolic profiling of mutants. The most potent holi mutant is defective in a subunit of cellulose synthase encoded by IRREGULAR XYLEM 3, and comparative analysis of this and other cell-wall mutants establishes a link between secondary cell-wall integrity and early chloroplast development, possibly involving altered ABA metabolism or sensing.


Asunto(s)
Arabidopsis/metabolismo , Celulosa/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Pared Celular/metabolismo , Cloroplastos/metabolismo , Regulación de la Expresión Génica de las Plantas , Lincomicina/metabolismo
16.
Biotechnol J ; 15(1): e1900174, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31468703

RESUMEN

Lincosamides (LMs), include clindamycin (CLIN), lincomycin (LIN), and pirlimycin (PIR), that are widely used as veterinary drugs. LM residues in edible animal origin foods endanger human health and are in urgent need of establishing fast, simple, and highly sensitive detection methods. A gold immunochromatographic strip is prepared to detect CLIN, LIN, and PIR residues simultaneously with a single monoclonal antibody. This antibody is obtained with the design of a novel Hapten and can simultaneously recognize CLIN, LIN, and PIR. Under optimized conditions, the strip results can be semi-quantitatively evaluated with the naked eye within 15 min, with cut-off values in phosphate-buffered saline of 1 ng mL-1 for CLIN, 10 ng mL-1 for LIN, and 25 ng mL-1 for PIR, respectively. Besides, the strip can also be quantified using a hand-held strip scanner, and the spiked samples are used for establishing matrix curves. The limits of detection for CLIN, LIN, and PIR in spiked milk, egg, beef, and honey samples can satisfy the detection requirement. The utility of this strip is also confirmed by positive honey sample. In short, this strip should be expected to be a useful tool for the rapid on-site screening of lincosamide residues in milk, egg, beef, and honey samples.


Asunto(s)
Residuos de Medicamentos/análisis , Análisis de los Alimentos/métodos , Inmunoensayo/métodos , Lincomicina/análisis , Animales , Bovinos , Residuos de Medicamentos/aislamiento & purificación , Huevos/análisis , Oro , Miel/análisis , Límite de Detección , Lincomicina/aislamiento & purificación , Leche/química , Carne Roja/análisis , Reproducibilidad de los Resultados
17.
Environ Pollut ; 256: 113392, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31662263

RESUMEN

Lincomycin mycelial residues (LMRs) are one kind of byproduct of the pharmaceutical industry. Hydrothermal treatment has been used to dispose of them and land application is an attractive way to reuse the treated LMRs. However, the safe dose for soil amendment remains unclear. In this study, a lab-scale incubation experiment was conducted to investigate the influence of the amendment dosage on lincomycin resistance genes and soil bacterial communities via quantitative PCR and 16S rRNA sequencing. The results showed that introduced lincomycin degraded quickly in soil and became undetectable after 50 days. Degradation rate of the high amendment amount (100 mg kg-1) was almost 4 times faster than that of low amendment amount (10 mg kg-1). Moreover, the introduced LMRs induced the increase of lincomycin resistance genes after incubation for 8 days, and two genes (lmrA and lnuB) showed a dosage-related increase. For example, the abundance of gene lmrA was 17.78, 74.13 and 128.82 copies g-1 soil for lincomycin concentration of 10, 50 and 100 mg kg-1, respectively. However, the abundance of lincomycin resistance genes recovered to the control level as the incubation period extended to 50 days, indicating a low persistence in soil. In addition, LMRs application markedly shifted the bacterial composition and significant difference was found between control soil, 10 mg kg-1 and 50 mg kg-1 lincomycin amended soil. Actually, several genera bacteria were significantly related to the elevation of lincomycin resistance genes. These results provided a comprehensive understanding of the effects of lincomycin dosage on the fate of resistance genes and microbial communities in LMRs applied soil.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Lincomicina/análisis , Microbiota/efectos de los fármacos , Micelio/química , Microbiología del Suelo , Contaminantes del Suelo/análisis , Lincomicina/toxicidad , Microbiota/genética , ARN Ribosómico 16S , Suelo/química , Contaminantes del Suelo/toxicidad
18.
J Biol Chem ; 295(51): 17816-17826, 2020 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-33454016

RESUMEN

Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment-protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.


Asunto(s)
Arabidopsis/metabolismo , Complejos de Proteína Captadores de Luz/metabolismo , Tilacoides/metabolismo , Arabidopsis/efectos de los fármacos , Cinética , Complejos de Proteína Captadores de Luz/química , Complejos de Proteína Captadores de Luz/genética , Complejos de Proteína Captadores de Luz/aislamiento & purificación , Lincomicina/farmacología , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/metabolismo , Multimerización de Proteína , Espectrometría de Fluorescencia , Ultracentrifugación , Xantófilas/química , Xantófilas/metabolismo , Zeaxantinas/química , Zeaxantinas/metabolismo
19.
Molecules ; 24(24)2019 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-31817501

RESUMEN

Lincomycin, monensin, and roxarsone are commonly used veterinary drugs. This study investigated their behaviours in different soils and their toxic effects on environmental organisms. Sorption and mobility analyses were performed to detect the migration capacity of drugs in soils. Toxic effects were evaluated by inhibition or acute toxicity tests on six organism species: algae, plants, daphnia, fish, earthworms and quails. The log Kd values (Freundlich model) of drugs were: lincomycin in laterite soil was 1.82; monensin in laterite soil was 2.76; and roxarsone in black soil was 1.29. The Rf value of lincomycin, roxarsone, monensin were 0.4995, 0.4493 and 0.8348 in laterite soil, and 0.5258, 0.5835 and 0.8033 in black soil, respectively. The EC50 for Scenedesmus obliquus, Arabidopsis thaliana, Daphnia magna and LC50/LD50 for Eisenia fetida, Danio rerio, and Coturnix coturnix were: 13.15 mg/L,32.18 mg/kg dry soil,292.6 mg/L,452.7 mg/L,5.74 g/kg dry soil and 103.9 mg/kg (roxarsone); 1.085 mg/L, 25 mg/kg dry soil, 21.1 mg/L, 4.76 mg/L, 0.346 g/kg dry soil and 672.8 mg/kg (monensin); 0.813 mg/L, 35.40 mg/kg dry soil, >400 mg/L, >2800 mg/L, >15 g/kg dry soil, >2000 mg/kg (lincomycin). These results showed that the environmental effects of veterinary drug residues should not be neglected, due to their mobility in environmental media and potential toxic effects on environmental organisms.


Asunto(s)
Arabidopsis/metabolismo , Coturnix/metabolismo , Daphnia/metabolismo , Lincomicina , Monensina , Oligoquetos/metabolismo , Roxarsona , Scenedesmus/metabolismo , Pez Cebra/metabolismo , Animales , Lincomicina/efectos adversos , Lincomicina/farmacocinética , Monensina/administración & dosificación , Monensina/farmacocinética , Roxarsona/efectos adversos , Roxarsona/farmacocinética
20.
J Phys Chem Lett ; 10(23): 7340-7346, 2019 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-31710503

RESUMEN

The photosynthetic apparatus of plants is a robust self-adjustable molecular system, able to function efficiently under varying environmental conditions. Under strong sunlight, it switches into photoprotective mode to avoid overexcitation by safely dissipating the excess absorbed light energy via nonphotochemical quenching (NPQ). Unfortunately, heterogeneous organization and simultaneous occurrence of multiple processes within the thylakoid membrane impede the study of natural NPQ under in vivo conditions; thus, usually artificially prepared antennae have been studied instead. However, it has never been shown directly that the origin of fluorescence quenching observed in these artificial systems underlies natural NPQ. Here we report the time-resolved fluorescence measurements of the dark-adapted and preilluminated-to induce NPQ-intact chloroplasts, performed over a broad temperature range. We show that their spectral response matches that observed in the LHCII aggregates, thus demonstrating explicitly for the first time that the latter in vitro system preserves essential properties of natural photoprotection.


Asunto(s)
Cloroplastos/metabolismo , Complejos de Proteína Captadores de Luz/metabolismo , Fotosíntesis , Arabidopsis/metabolismo , Cloroplastos/efectos de los fármacos , Luz , Complejos de Proteína Captadores de Luz/química , Lincomicina/farmacología , Fotosíntesis/efectos de los fármacos , Plantas/metabolismo , Espectrometría de Fluorescencia , Temperatura
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