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1.
Chemosphere ; 247: 125837, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31927185

RESUMO

Application of low dosage of H2O2 at early stage of cyanobacterial life cycle is a promising route for cyanobacterial bloom mitigation, which could minimize adverse effects on non-target organisms. Besides, influence of co-existing contaminants on cyanobacterial bloom mitigation under combined pollution conditions remains unclear. This study assessed the influence of a mixture of four frequently detected antibiotics (tetracycline, sulfamethoxazole, ciprofloxacin and amoxicillin) during H2O2 treatment of Microcystis aeruginosa at early growth stage. H2O2 significantly (p < 0.05) inhibited growth rate, chlorophyll a content, Fv/Fm and rETRmax in a dose-dependent manner at low doses of 0.25-1 mg L-1, through downregulating proteins involved in cell division, cellular component organization, gene expression and photosynthesis. Although H2O2 increased microcystin content in each cyanobacterial cell through the upregulation of microcystin synthetases (mcyC and mcyF), total microcystin concentration in H2O2 treated groups was significantly (p < 0.05) reduced due to the decrease of cell density. Existence of 80 and 200 ng L-1 mixed antibiotics during H2O2 treatment facilitated the scavenging of ROS by antioxidant enzymes and significantly (p < 0.05) stimulated growth, photosynthesis, microcystin synthesis and microcystin release in H2O2 treated cells, through the upregulation of proteins involved in photosynthesis, oxidation-reduction process, biosynthesis, gene expression and transport. Mixed antibiotics increased the hazard of M. aeruginosa during H2O2 treatment, through the stimulation of microcystin synthesis and release at the proteomic level. Each target antibiotic should be controlled below 5 ng L-1 before the application of H2O2 for eliminating the interference of antibiotics on cyanobacterial bloom mitigation.


Assuntos
Antibacterianos/farmacologia , Peróxido de Hidrogênio/farmacologia , Microcystis/efeitos dos fármacos , Proteômica/métodos , Amoxicilina/farmacologia , Clorofila A , Ciprofloxacino/metabolismo , Cianobactérias/efeitos dos fármacos , Microcistinas/biossíntese , Microcystis/metabolismo , Oxirredução , Fotossíntese/efeitos dos fármacos , Sulfametoxazol/metabolismo
2.
Environ Res ; 183: 109154, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31986431

RESUMO

Ciprofloxacin is a pharmaceutically active compound which belongs to a class of micropollutants that cannot be removed using conventional water treatment systems. In this study, photocatalytic degradation using materials with high surface area and active sites was proposed to remove such contaminants. We demonstrated an easily scalable and simple synthesis route to prepare a 3D porous sulfur-doped g-C3N4/ZnO hybrid material, and the preparation process parameters were optimized using response surface methodology targeting Ciprofloxacin degradation. The hybrid material removed up to 98% of the bio-toxic Ciprofloxacin from synthetic water. The porous, defect engineered, thermally stable, and chemically interconnected hybrid material presented an 18 and 38% improved degradation efficiency compared to ZnO and sulfur-doped g-C3N4 (or S-C3N4), respectively. Based on our experimental results, an empirical relation correlating synthesis process parameters and degradation efficiency was developed using face-centered central composite design (FCCD) and response surface methodology (RSM). The current model can be used to design catalytic materials for removing bio-toxic and other micropollutants from water.


Assuntos
Ciprofloxacino , Óxido de Zinco , Catálise , Ciprofloxacino/metabolismo , Nanotecnologia , Porosidade , Enxofre
3.
Environ Pollut ; 257: 113578, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31806458

RESUMO

The residual characteristics and the adsorption-desorption behaviors of azoxystrobin (AZO) as well as the soil ecological effects in the individual repeated treatments of AZO and its combination with chlorothalonil (CTL), chlortetracycline (CTC) and ciprofloxacin (CIP) were systematically studied in organic manure (OM)-amended soil under laboratory conditions. The presence of CTL, CTC, and CIP, both individually and combined, decreased the sorption affinity of AZO with the Freundlich adsorption and desorption coefficient decreasing by 0.3-24.2%, and CTC and CIP exhibited greater adverse effects than CTL. AZO dissipated slowly and the residues significantly accumulated during ten repeated treatments. The dissipation of AZO was inhibited to different degrees in the combined treatments. Biolog analysis revealed that the soil microbial functional diversity in the OM-soil + AZO and OM-soil + AZO + CTL treatments was higher than that in the OM-soil treatment during the former three repeated treatments, but which was inhibited during the latter seven repeated treatments. The soil microbial functional diversity in the OM-soil + AZO + CTC, OM-soil + AZO + CIP and OM-soil + AZO + CTL + CTC + CIP treatments was inhibited during the ten repeated treatments compared with OM-soil treatment. Metagenomic results showed that all repeated treatments significantly increased the relative abundance of Actinobacteria, but significantly decreased that of Proteobacteria and Firmicutes during the ten repeated treatments. Furthermore, the relative abundance of soil dominant bacterial genera Rhodococcus, Mycobacterium and Arthrobacter in all the repeated treatments significantly increased by 1.5-1283.9% compared with the OM-soil treatment. It is concluded that coexistence of CTL, CTC and CIP, both individually and combined, with AZO can inhibit the dissipation of AZO, reduce the adsorption affinity of AZO on soil, and alter the soil microbial community structure and functional diversity.


Assuntos
Antibacterianos/farmacologia , Bactérias/metabolismo , Clortetraciclina/farmacologia , Ciprofloxacino/farmacologia , Microbiota/efeitos dos fármacos , Nitrilos/farmacologia , Microbiologia do Solo , Poluentes do Solo/análise , Bactérias/efeitos dos fármacos , Clortetraciclina/metabolismo , Ciprofloxacino/metabolismo , Esterco , Nitrilos/metabolismo , Pirimidinas , Solo/química , Estrobilurinas
4.
J Colloid Interface Sci ; 560: 701-713, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706655

RESUMO

Photocatalysis technology is regarded as a promising way for environmental remediation, but rationally designing photocatalysis system with high-speed interfacial charge transfer, sufficient photoabsorption and surface reactive sites is still a challenge. In this study, anchoring single-unit-cell defective Bi2MoO6 on ultrathin g-C3N4 to form 2D/2D heterostructure system is a triple-purpose strategy for high-performance photocatalysis. The defect structure broadens photo-responsive range. The large intimate contact interface area between two monomers promotes charges carrier transfer. The enhanced specific surface area exposes more reactive sites for mass transfer and catalytic reaction. As a result, the obtained heterostructure displays excellent photocatalytic performance for ciprofloxacin (CIP) (0.0126 min-1), which is 3.32 and 2.93 folds higher than Bi2MoO6 and g-C3N4. In addition, this heterostructure retains high-performance for actual wastewaters treatment, and it displays strong mineralization ability. And this heterojunction also exhibits excellent photostability based on cyclic experiment. Mechanism exploration reveals that hole, superoxide radical, and hydroxyl radical are chief reactive species toward CIP degradation, thereby a Z-scheme charge carrier transfer channel is proposed. In addition, the intermediates and degradation pathways of CIP are tracked by liquid chromatography-triple quadrupole tandem mass spectrometry (LCMS/MS) and three-dimensional excitation-emission matrix fluorescence spectroscopy (3D EEMs). This study paves new way to design and construct atomic level 2D/2D heterojunction system for environment remediation.


Assuntos
Antibacterianos/química , Bismuto/química , Ciprofloxacino/química , Nanopartículas Metálicas/química , Molibdênio/química , Nanoestruturas/química , Nitrilos/química , Antibacterianos/metabolismo , Catálise , Ciprofloxacino/metabolismo , Luz , Nanopartículas Metálicas/efeitos da radiação , Molibdênio/efeitos da radiação , Nanoestruturas/efeitos da radiação , Nitrilos/efeitos da radiação , Processos Fotoquímicos , Fotólise
5.
Environ Geochem Health ; 42(6): 1531-1541, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31420762

RESUMO

This study investigated the effects and fate of the antibiotic ciprofloxacin (CIP) at environmentally relevant levels (50-500 µg/L) in activated sludge (AS) microbial communities under aerobic conditions. Exposure to 500 µg/L of CIP decreased species diversity by about 20% and significantly altered the phylogenetic structure of AS communities compared to those of control communities (no CIP exposure), while there were no significant changes upon exposure to 50 µg/L of CIP. Analysis of community composition revealed that exposure to 500 µg/L of CIP significantly reduced the relative abundance of Rhodobacteraceae and Nakamurellaceae by more than tenfold. These species frequently occur in AS communities across many full-scale wastewater treatment plants and are involved in key ecosystem functions (i.e., organic matter and nitrogen removal). Our analyses showed that 50-500 µg/L CIP was poorly removed in AS (about 20% removal), implying that the majority of CIP from AS processes may be released with either their effluents or waste sludge. We therefore strongly recommend further research on CIP residuals and/or post-treatment processes (e.g., anaerobic digestion) for waste streams that may cause ecological risks in receiving water bodies.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Microbiota/efeitos dos fármacos , Esgotos/microbiologia , Poluentes Químicos da Água/farmacologia , Actinobacteria/efeitos dos fármacos , Antibacterianos/metabolismo , Reatores Biológicos , Ciprofloxacino/metabolismo , Microbiota/fisiologia , Filogenia , RNA Ribossômico 16S , Rhodobacteraceae/efeitos dos fármacos , Esgotos/química , Eliminação de Resíduos Líquidos/instrumentação , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Poluentes Químicos da Água/metabolismo
6.
Aquat Toxicol ; 219: 105374, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862549

RESUMO

Phytoremediation is an effective and environmentally friendly approach to treat antibiotic contaminated water, however, the mechanisms of migration and transformation of antibiotics in plant tissues are still far from clear. In this study, the floating macrophyte Eichhornia crassipes was exposed to a series of antibiotic ciprofloxacin (CIP) concentrations. The results showed that the CIP was taken up and accumulated in the roots, which were the major accumulative tissue. CIP content increased with lipid content. During cultivation, the root bioconcentration factor (RCF) gradually increased. The average CIP content detected in aerial parts was 12.80 µg g-1, an order of magnitude lower than in the roots. At low CIP concentrations, the highest leaf bioconcentration factor (LCF) and transfer factor (TF) indicated highly efficient translocation from roots to aerial parts. The soluble protein growth rate of leaves, which is associated with metabolic activity, increased following CIP exposure. Overall, eight major transformation products in E. crassipes tissues were identified, and three possible transformation pathways were proposed involving the processes of desethylation, dehydroxylation, oxidation, hydroxylation and cleavage of the piperazine and quinoline rings. These findings could prove beneficial for improving the management or amelioration methods used for treating water contaminated with antibiotics.


Assuntos
Antibacterianos/análise , Bioacumulação , Ciprofloxacino/análise , Eichhornia/efeitos dos fármacos , Poluentes Químicos da Água/análise , Antibacterianos/metabolismo , Biodegradação Ambiental , Biotransformação , Ciprofloxacino/metabolismo , Eichhornia/metabolismo , Poluentes Químicos da Água/metabolismo
7.
Equine Vet J ; 52(1): 136-143, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31009093

RESUMO

BACKGROUND: A recent study demonstrated that enrofloxacin and ciprofloxacin cross the equine placenta without causing gross cartilage or tendon lesions in the 9-month fetus; however, long-term effects of in utero fluoroquinolone exposure remain unknown. OBJECTIVES: To assess effects of fetal exposure to enrofloxacin on the resulting foal's cartilage and tendon strength. STUDY DESIGN AND METHODS: Healthy mares at 280 days' gestation were allocated into four groups: untreated (n = 5), therapeutic treatment (7.5 mg/kg enrofloxacin, PO × 14 days, n = 6), supratherapeutic treatment (15 mg/kg, PO × 14 days, n = 6) and no mare treatment with treatment of the foals post-partum (n = 2). Mares were allowed to carry pregnancy to term, and foals were maintained on pasture for 5 weeks. After that foals were euthanized, and their articular cartilage and extensor and flexor tendons were examined macroscopically and histologically for lesions. Tendon strength was tested by loading until failure. RESULTS: Administration of enrofloxacin at recommended doses in late gestation did not result in cartilaginous lesions or clinical lameness in any foal by 5 weeks old. Tensile strength was greater in hind tendons than front tendons, but no difference was found between foals born from treated and control mares. Expectedly, osteochondral changes were present both in foals born from enrofloxacin-treated mares and in negative control foals with no apparent association with fluoroquinolone treatment during pregnancy. MAIN LIMITATIONS: Only one time point in gestation was evaluated, and mares treated in the study were healthy at time of treatment. Additionally, it is possible that the assessments performed herein were not sensitive enough to detect subtle or functional changes in the articular cartilage. Further studies are needed to determine if enrofloxacin administration during late pregnancy potentiates osteochondral alterations in the first year of life. CONCLUSIONS: While this study did not assess other stages of gestation or long-term foal outcomes, short-term administration of enrofloxacin to late gestation mares did not result in macroscopic or microscopic lesions in the resulting foals by 5 weeks of age.


Assuntos
Enrofloxacina/efeitos adversos , Doenças dos Cavalos/etiologia , Complicações na Gravidez/veterinária , Prenhez , Animais , Animais Recém-Nascidos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Fenômenos Biomecânicos , Ciprofloxacino/efeitos adversos , Ciprofloxacino/metabolismo , Relação Dose-Resposta a Droga , Enrofloxacina/administração & dosagem , Feminino , Cavalos , Gravidez , Complicações na Gravidez/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Tendões/efeitos dos fármacos , Tendões/patologia
8.
J Vet Pharmacol Ther ; 43(1): 19-25, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31271466

RESUMO

To the best of the authors' knowledge, pharmacokinetic information to establish suitable therapeutic plans for freshwater crocodiles is limited. Therefore, the purpose of this study was to clarify the pharmacokinetic characteristics of enrofloxacin (ENR) in freshwater crocodiles, Crocodylus siamensis, following single intravenous and intramuscular administration at a dosage of 5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. The plasma concentrations of ENR and its metabolite ciprofloxacin (CIP) were measured by liquid chromatography tandem-mass spectrometry. The concentrations of ENR and CIP in the plasma were quantified up to 144 hr after both the administrations. The half-life was long (43-44 hr) and similar after both administrations. The absolute i.m. bioavailability was 82.65% and the binding percentage of ENR to plasma protein ranged from 9% to 18% with an average of 10.6%. Percentage of CIP (plasma concentrations) was 15.9% and 19.9% after i.v. and i.m. administration, respectively. Based on the pharmacokinetic data, susceptibility break point and PK-PD indexes, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be appropriate for treatment of susceptible bacteria (MIC > 1 µg/mL) in freshwater crocodiles, C. siamensis.


Assuntos
Jacarés e Crocodilos , Antibacterianos/farmacocinética , Ciprofloxacino/metabolismo , Ciprofloxacino/farmacocinética , Enrofloxacina/farmacocinética , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/metabolismo , Área Sob a Curva , Ciprofloxacino/administração & dosagem , Enrofloxacina/administração & dosagem , Meia-Vida , Injeções Intramusculares , Injeções Intravenosas , Masculino
9.
J Mater Chem B ; 7(25): 3982-3992, 2019 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-31681475

RESUMO

The kinetics of drug release from hydroxyapatite (HAp) cements could be tuned by controlling the kinetics of crystallization of their HAp precursor powders during synthesis. Here it is shown that this history of formation affects not only the kinetics, but also the mechanism of release. Cements composed of two HAp powders precipitated under different conditions, one (HAp2) taking twice longer to transform from the amorphous to the crystalline state than the other (HAp1), were mixed at different ratios to tune their drug release kinetics and tested for the release mechanism in conjunction with compositional and microstructural analyses. While the cement component converting to the amorphous phase during gelation (HAp2) exhibited a faster, but also more anomalous, non-Fickian mechanism of release of vancomycin, the cement component retaining its crystalline state all throughout gelation, setting and hardening (HAp1) stabilized at the ideal, Fickian diffusion case corresponding to the Korsmeyer-Peppas exponent value of 0.45 ± 0.02. This effect got reversed for the other antibiotic studied as a drug, ciprofloxacin, in which case HAp2 exhibited the ideal, Fickian diffusion with n = 0.45 ± 0.02 and the increase in the content of the cement component retaining its crystallinity during gelation, setting and hardening (HAp1) steadily shifted the mechanism of release to more anomalous, non-Fickian types. This has indicated that the molecular structure of the drug is an essential determinant of the mechanism of release and that the design of a carrier for a universally tunable release of drugs based on the passive transport is likely impossible. Preliminary assays involving the addition of chitosan or gelatin as polymeric components to HAp led to the inclusion of swelling and erosion as additional effects by which the drug escapes the carrier and shifted the release toward less diffusional and more multimodal mechanisms. With regard to the microstructural and compositional effects governing the release mechanism and kinetics, the retention of a finite concentration of slit-like pores of the amorphous precursor in HAp2 and its lower surface energy and lesser drug binding potential in the gelled, amorphous state, but also its possibly less stable and more diffusive particle surface and higher structural water content were elaborated as potential reasons explaining the distinct rates and mechanisms of release from the two HAp powders with different histories of formation.


Assuntos
Antibacterianos/química , Fosfatos de Cálcio/química , Hidroxiapatitas/química , Nanoestruturas/química , Antibacterianos/metabolismo , Quitosana/química , Ciprofloxacino/química , Ciprofloxacino/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Gelatina/química , Concentração de Íons de Hidrogênio , Cinética , Vancomicina/química , Vancomicina/metabolismo
10.
Microb Genom ; 5(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31580793

RESUMO

Yersinia pseudotuberculosis is a Gram-negative bacterium capable of causing gastrointestinal infection and is closely related to the highly virulent plague bacillus Yersinia pestis. Infections by both species are currently treatable with antibiotics such as ciprofloxacin, a quinolone-class drug of major clinical importance in the treatment of many other infections. Our current understanding of the mechanism of action of ciprofloxacin is that it inhibits DNA replication by targeting DNA gyrase, and that resistance is primarily due to mutation of this target site, along with generic efflux and detoxification strategies. We utilized transposon-directed insertion site sequencing (TraDIS or TnSeq) to identify the non-essential chromosomal genes in Y. pseudotuberculosis that are required to tolerate sub-lethal concentrations of ciprofloxacin in vitro. As well as highlighting recognized antibiotic resistance genes, we provide evidence that multiple genes involved in regulating DNA replication and repair are central in enabling Y. pseudotuberculosis to tolerate the antibiotic, including DksA (yptb0734), a regulator of RNA polymerase, and Hda (yptb2792), an inhibitor of DNA replication initiation. We furthermore demonstrate that even at sub-lethal concentrations, ciprofloxacin causes severe cell-wall stress, requiring lipopolysaccharide lipid A, O-antigen and core biosynthesis genes to resist the sub-lethal effects of the antibiotic. It is evident that coping with the consequence(s) of antibiotic-induced stress requires the contribution of scores of genes that are not exclusively engaged in drug resistance.


Assuntos
Ciprofloxacino/farmacologia , Resistência Microbiana a Medicamentos/genética , Yersinia pseudotuberculosis/genética , Anti-Infecciosos/farmacologia , Sequência de Bases/genética , Cromossomos/genética , Ciprofloxacino/metabolismo , Reparo do DNA/genética , Replicação do DNA/genética , Evolução Molecular , Genoma Bacteriano , Mutação , Virulência/genética , Fatores de Virulência/genética , Yersinia pestis/genética , Yersinia pestis/metabolismo , Yersinia pseudotuberculosis/metabolismo , Infecções por Yersinia pseudotuberculosis/microbiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-31540337

RESUMO

To improve the biodegradation efficiency of fluoroquinolone antibiotics during sewage treatment, fluoroquinolone aerobic, anaerobic and facultative degrading enzymes for fluoroquinolone degradation were modified by molecular docking and homology modelling. First, amino acid residues of the binding sites of degrading enzymes for the target fluoroquinolones ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL) were analysed by the molecular docking method. The hydrophobic amino acid residues within 5 Å of the target fluoroquinolone molecules were selected as the modification sites. The hydrophobic amino acid residues at the modified sites were replaced by the hydrophilic amino acid residues, and 150 amino acid sequence modification schemes of the degrading enzymes were designed. Subsequently, a reconstruction scheme of the degrading enzyme amino acid sequence reconstruction scheme was submitted to the SWISS-MODEL server and a selected homology modelling method was used to build a new structure of the degrading enzyme. At the same time, the binding affinities between the novel degrading enzymes and the target fluoroquinolones (represented by the docking scoring function) were evaluated by the molecular docking method. It was found that the novel enzymes can simultaneously improve the binding affinities for the three target fluoroquinolones, and the degradation ability of the six modification schemes was increased by more than 50% at the same time. Among the novel enzymes, the affinity effect of the novel anaerobic enzyme (6-1) with CIP, NOR and OFL was significantly increased, with increases of 129.24%, 165.06% and 169.59%, respectively, followed by the facultative enzyme and aerobic enzyme. In addition, the designed degrading enzymes had certain selectivity for the degradation of the target quinolone. Among the novel enzymes, the binding affinities of the novel anaerobic enzyme (6-3) and CIP, the novel aerobic enzyme (3-6) and NOR, and the novel facultative enzyme (13-6) and OFL were increased by 149.71%, 178.57% and 297.12% respectively. Calculations using the Gaussian09 software revealed that the degradation reaction barrier of the novel degrading enzyme (7-1) and CIP NOR and OFL decreased by 37.65 kcal·mol-1, 6.28 kcal·mol-1 and 6.28 kcal·mol-1, respectively, which would result in efficient degradation of the target fluoroquinolone molecules. By analysing the binding affinity of the degrading enzymes before and after the modification with methanol, it was further speculated that the degradation effect of the modified aerobic degrading enzymes on organic matter was lower than that before the modification, and the increase or decrease in the degradation effect was less than 10%. The mechanism analysis found that the interaction between the modified amino acid residues of the degrading enzymes and the fluoroquinolone molecules increased. The average distance between the amino acid residues and the fluoroquinolone molecules represented a comprehensive affinity effect, and its value was positively correlated with the degradation effect of the novel degrading enzymes.


Assuntos
Antibacterianos/metabolismo , Ciprofloxacino/metabolismo , Modelos Moleculares , Norfloxacino/metabolismo , Ofloxacino/metabolismo , Aminoácidos/metabolismo , Antibacterianos/química , Sítios de Ligação , Biodegradação Ambiental , Ciprofloxacino/química , Norfloxacino/química , Ofloxacino/química
12.
Chemosphere ; 237: 124421, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31382196

RESUMO

Antibiotics in the effluents of municipal wastewater treatment plants (WWTP) may create selective pressures to induce antibiotic resistance in bacteria downstream. This study evaluates ciprofloxacin (CIP) removal by a freshwater alga, Scenedesmus dimorphus, to assess the efficacy of algae-based tertiary treatment in reducing effluent-induced CIP resistance. Results show significant CIP removal in light-exposed samples without algae and experimental algae (EA) samples: 53% and 93%, respectively, over 144 h. A residual antibiotic potency assay reveals that untreated CIP is significantly more growth-inhibiting to a model bacterium (Escherichia coli) than the algae-treated and light-exposed samples during short exposures (6 h). Adaptive laboratory evolution (ALE), again using E. coli, reveals that treated samples exhibit reduced capacity to elicit CIP resistance during sustained exposures compared to untreated CIP. Finally, observed CIP resistance in the CIP-exposed ALE lineages is corroborated via genotype characterization, which reveals the presence of resistance-associated mutations in gyrase subunit A (gyrA) that are not present in ALE lineages exposed to algae treated or light-exposed samples. As such, algae-mediated tertiary treatment could be effective in suppressing CIP resistance in bacterial communities downstream from WWTP. In addition, ALE is useful for assessing the potential of wastewater-relevant samples to elicit antibiotic resistance downstream.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Scenedesmus/metabolismo , Eliminação de Resíduos Líquidos/métodos , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Ciprofloxacino/isolamento & purificação , Ciprofloxacino/metabolismo , DNA Girase/genética , Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Genótipo , Testes de Sensibilidade Microbiana , Mutação , Águas Residuárias/química , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/farmacologia
13.
ACS Chem Biol ; 14(11): 2453-2462, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31464417

RESUMO

Lon is a widely conserved housekeeping protease found in all domains of life. Bacterial Lon is involved in recovery from various types of stress, including tolerance to fluoroquinolone antibiotics, and is linked to pathogenesis in a number of organisms. However, detailed functional studies of Lon have been limited by the lack of selective, cell-permeant inhibitors. Here, we describe the use of positional scanning libraries of hybrid peptide substrates to profile the primary sequence specificity of bacterial Lon. In addition to identifying optimal natural amino acid binding preferences, we identified several non-natural residues that were leveraged to develop optimal peptide substrates as well as a potent peptidic boronic acid inhibitor of Lon. Treatment of Escherichia coli with this inhibitor promotes UV-induced filamentation and reduces tolerance to ciprofloxacin, phenocopying established lon-deletion phenotypes. It is also nontoxic to mammalian cells due to its selectivity for Lon over the proteasome. Our results provide new insight into the primary substrate specificity of Lon and identify substrates and an inhibitor that will serve as useful tools for dissecting the diverse cellular functions of Lon.


Assuntos
Inibidores Enzimáticos/química , Proteínas de Escherichia coli/antagonistas & inibidores , Oligopeptídeos/química , Biblioteca de Peptídeos , Protease La/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Ácidos Borônicos/química , Ciprofloxacino/metabolismo , Inibidores Enzimáticos/metabolismo , Escherichia coli , Proteínas de Escherichia coli/genética , Humanos , Camundongos , Mutação , Oligopeptídeos/metabolismo , Protease La/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Células RAW 264.7 , Relação Estrutura-Atividade , Especificidade por Substrato
14.
Environ Sci Pollut Res Int ; 26(29): 30348-30355, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31435908

RESUMO

Antibiotic residues pose a threat to the health of aquatic organisms. The effects and accumulation of antibiotic ciprofloxacin (CIP) in a floating macrophyte (Eichhornia crassipes) under hydroponic conditions were investigated. It was found that E. crassipes exposure to CIP (< 1000 µg L-1) could maintain a stable photosynthesis efficiency. In response to CIP stress, catalase and peroxidase activities of leaves were 7.24-37.51 nmol min-1 g-1 and 98.46-173.16 U g-1, respectively. The presence of CIP did not inhibit the growth of the plant. After 14 days of exposure, tender leaves became white and withered, ascribed to the decline of chlorophyll content and chlorophyll fluorescence parameters. The CIP concentrations, absorbed by E. crassipes, were highest in the roots, followed by white aerial parts and green aerial parts at CIP concentrations of 100 and 1000 µg L-1. These findings demonstrated that E. crassipes could absorb and tolerate CIP in a limited time-scale and imply an alternative solution for phytoremediation in water bodies contaminated with antibiotics.


Assuntos
Antibacterianos/análise , Organismos Aquáticos/efeitos dos fármacos , Ciprofloxacino/análise , Eichhornia/efeitos dos fármacos , Poluentes Químicos da Água/análise , Antibacterianos/metabolismo , Organismos Aquáticos/crescimento & desenvolvimento , Organismos Aquáticos/metabolismo , Biodegradação Ambiental , Clorofila/metabolismo , Ciprofloxacino/metabolismo , Ecotoxicologia , Eichhornia/crescimento & desenvolvimento , Eichhornia/metabolismo , Hidroponia , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Poluentes Químicos da Água/metabolismo
15.
Bioelectrochemistry ; 130: 107330, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31323489

RESUMO

In the present investigation the electrochemical behaviour of the drug, Ciprofloxacin (Cf) and its interaction with the Bovine Serum Albumin (BSA) is reported. UV-Visible Spectroscopy (UV-Vis) and Spectro-electrochemical measurements were carried out to quantify the charge transfer process in Cf. Analysis of the results obtained from cyclic voltammetry (CV) measurements indicated the electrochemical oxidation of Cf followed mixed adsorption and diffusion control process. The spectro-electrochemical investigations were carried out and the modification of the spectral peaks were monitored to obtain the mechanism of the electrochemical oxidation process of Cf. Interaction of Cf with Bovine Serum Albumin (BSA) were investigated using electrochemical, spectroscopic and spectro-electrochemical experiments. Important electro-kinetic parameters like; the electron transfer property, binding constant and diffusivity of the Cf/BSA complex were investigated. Electrochemistry with an ultra-microelectrode was utilised to investigate the diffusivity of the drug and its complex with BSA, which supports the strong binding of Cf with BSA.


Assuntos
Antibacterianos/metabolismo , Ciprofloxacino/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Antibacterianos/química , Bovinos , Ciprofloxacino/química , Técnicas Eletroquímicas , Ligação Proteica , Espectrofotometria Ultravioleta
16.
Appl Microbiol Biotechnol ; 103(17): 6933-6948, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332486

RESUMO

Although internationally recognized as the "highest priority critically important antimicrobials," fluoroquinolones are extensively used in both human and veterinary medicine. Poor metabolism and recalcitrance of fluoroquinolones have led to their worldwide presence in municipal wastewaters as well as in manure and, consequently, in several environmental compartments. Being one of the most widely used fluoroquinolones in human medicine and, aside from that, the main metabolite of the veterinary drug enrofloxacin, ciprofloxacin is the most frequently detected fluoroquinolone in effluents of European wastewater treatment plants. Due to serious global concerns about the increasing emergence of bacterial (multi)resistances toward the highly efficient fluoroquinolones, special attention has been paid to their environmental degradation by various microorganisms. This review summarizes research on microbial transformation and degradation of fluoroquinolones with special emphasis on ciprofloxacin, presents an overview of the main ciprofloxacin biotransformation products, and takes a closer look at their biological relevance. Furthermore, own data, experiences, and publications gathered from our recent research in the field are acknowledged.


Assuntos
Antibacterianos/metabolismo , Ciprofloxacino/metabolismo , Poluentes Ambientais/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Biodegradação Ambiental , Biotransformação , Ciprofloxacino/química , Ciprofloxacino/farmacologia , Poluentes Ambientais/química , Poluentes Ambientais/farmacologia , Fluoroquinolonas/química , Fluoroquinolonas/metabolismo , Fluoroquinolonas/farmacologia
17.
J Med Chem ; 62(9): 4411-4425, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31009558

RESUMO

Expression of ß-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to ß-lactam antibiotics. In this article, we describe the development of an antibiotic prodrug that combines ciprofloxacin with a ß-lactamase-cleavable motif. The prodrug is only bactericidal after activation by ß-lactamase. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically relevant E. coli isolates expressing diverse ß-lactamases; bactericidal activity was not observed in strains without ß-lactamase. These findings demonstrate that it is possible to exploit antibiotic resistance to selectively target ß-lactamase-producing bacteria using our prodrug approach, without adversely affecting bacteria that do not produce ß-lactamase. This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Ciprofloxacino/análogos & derivados , Ciprofloxacino/farmacologia , Pró-Fármacos/farmacologia , beta-Lactamases/metabolismo , Antibacterianos/síntese química , Antibacterianos/metabolismo , Cefalosporinas/síntese química , Cefalosporinas/metabolismo , Ciprofloxacino/metabolismo , Resistência Microbiana a Medicamentos/fisiologia , Escherichia coli/efeitos dos fármacos , Hidrólise , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pró-Fármacos/síntese química , Pró-Fármacos/metabolismo , Relação Estrutura-Atividade , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/metabolismo , Inibidores da Topoisomerase II/farmacologia
18.
Environ Pollut ; 249: 453-462, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30927690

RESUMO

The co-occurrence of aquatic contaminants, such as antibiotics and herbicides, has motivated investigations into their interactive effects on aquatic organisms. We examined the combined effects of environmental concentrations of the antibiotic Enrofloxacin (Enro; 0-2.25 µg l-1) and Roundup OriginalDI (Roundup®; 0-0.75 µg active ingredient l-1), a glyphosate based-herbicide, on Elodea canadensis. Enro alone was not toxic, but the plants were highly sensitive to Roundup® whose toxicity is related to the induction of oxidative stress. The metabolism of Enro by plants into Ciprofloxacin (Cipro) was observed, and although former is not phytotoxic, oxidative events associated with Cipro generation were observed. The activity of cytochrome P450 was shown to be involved in Enro degradation in E. canadensis. As a cytochrome P450 inhibitor, Roundup® decreases Enro metabolism in plants. Enro, in turn, increases glyphosate uptake and toxicity, so that Enro and Roundup® have synergistic effects, disrupting the physiological processes of E. canadensis. Our results suggest E. canadensis as a potential candidate for the reclamation of Enro in contaminated waters, but not for Roundup® due to its high sensitivity to that herbicide.


Assuntos
Biodegradação Ambiental , Enrofloxacina/toxicidade , Glicina/análogos & derivados , Herbicidas/toxicidade , Hydrocharitaceae/efeitos dos fármacos , Hydrocharitaceae/fisiologia , Animais , Antibacterianos/metabolismo , Ciprofloxacino/metabolismo , Glicina/toxicidade , Estresse Oxidativo/efeitos dos fármacos
19.
Biochimie ; 160: 24-27, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30763638

RESUMO

A Mg2+-water bridge between the C-3, C-4 diketo moiety of fluoroquinolones and the conserved amino acid residues in the GyrA/ParC subunit is critical for the binding of a fluoroquinolone to a topoisomerase-DNA covalent complex. The fluoroquinolone UING-5-249 (249) can bind to the GyrB subunit through its C7-aminomethylpyrrolidine group. This interaction is responsible for enhanced activities of 249 against the wild type and quinolone-resistant mutant topoisomerases. To further evaluate the effects of the 249-GyrB interaction on fluoroquinolone activity, we examined the activities of decarboxy- and thio-249 against DNA gyrase and conducted docking studies using the structure of a gyrase-ciprofloxacin-DNA ternary complex. We found that the 249-GyrB interaction rescued the activity of thio-249 but not that of decarboxy-249. A C7-group that binds more strongly to the GyrB subunit may allow for modifications at the C-4 position, leading to a novel compound that is active against the wild type and quinolone-resistant pathogens.


Assuntos
Ciprofloxacino/metabolismo , DNA Girase/metabolismo , DNA Bacteriano/metabolismo , Fluoroquinolonas/metabolismo , Pirrolidinas/química , Staphylococcus aureus/enzimologia , Compostos de Sulfidrila/química , Antibacterianos/química , Antibacterianos/metabolismo , Ciprofloxacino/química , DNA Girase/química , DNA Girase/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Descarboxilação , Escherichia coli/metabolismo , Fluoroquinolonas/química , Testes de Sensibilidade Microbiana , Subunidades Proteicas
20.
Sci Total Environ ; 665: 41-51, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30772572

RESUMO

Ciprofloxacin is a broad spectral and highly refractory antibiotic. It is an emerging pollutant. This study aimed to utilise co-metabolism as a means to degrade ciprofloxacin by a bacterial consortium. The stable bacterial consortium XG capable of efficiently degrading ciprofloxacin was successfully established through successive acclimation of indigenous microorganisms. The consortium XG was primarily consisted of Achromobacter, Bacillus, Lactococcus, Ochrobactrum, and Enterococcus as well as at least other five minor genera. A novel strain YJ17 with CIP-degrading ability was isolated from the consortium and identified as Ochrobactrum sp. The consortium XG utilised amino acids, carbohydrates, and carboxylic acids at a rate approximately 16.6-243-fold greater than the other carbon substrates, but only slow utilisation of ciprofloxacin as a sole carbon source. Ciprofloxacin can be co-metabolized along with many carbon sources, attaining degradation rates up to 63%. Glycyl-l-glutamic acid, d-cellobiose, and itaconic acid are among the substrates most favourable for co-metabolism. The metabolites of ciprofloxacin were identified by LC-QTOF-MS. Co-metabolic degradation of ciprofloxacin by consortium XG led to the removal of essential functional groups from parent compound, thus resulting in formation of metabolites with less bioactive potency. Finally, a possible biochemical pathway for the degradation of ciprofloxacin was proposed. Consortium XG possesses high potential for bioremediation of ciprofloxacin-contaminated environments in the presence of a co-substrate.


Assuntos
Biodegradação Ambiental , Ciprofloxacino/metabolismo , Poluentes Ambientais/metabolismo , Consórcios Microbianos , Antibacterianos/metabolismo , Ochrobactrum/metabolismo
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