Triclosan and triclocarban are antimicrobial compounds added to a variety of consumer products that are commonly detected in waste water effluent. The focus of this study was to determine whether the bioconcentration of these compounds in wetland plants and sediments exhibited species specific and site specific differences by collecting field samples from a constructed wetland in Denton, Texas. The study showed that species-specific differences in bioconcentration exist for triclosan and triclocarban. Site-specific differences in bioconcentration were observed for triclosan and triclocarban in roots tissues and sediments. These results suggest that species selection is important for optimizing the removal of triclosan and triclocarban in constructed wetlands and raises concerns about the long term exposure of wetland ecosystems to these compounds.

Les facteurs environnementaux appelés « perturbateurs endocriniens (PE) » semblent avoir un rôle dans le développement et la progression des cancers de la prostate (PCa). Il est bien établi que l'homéostasie calcique et l'activité des canaux ioniques sont impliquées dans la cancérogénèse prostatique et il est possible que ces PE favorisent la cancérogénèse en modulant la signalisation calcique. Dans ce contexte, nous avons étudié l’effet du bisphénol A (BPA) et du Triclosan (TCS) sur la signalisation calcique des cellules cancéreuses prostatiques humaines. Nous avons ainsi montré que le BPA pouvait induire la migration des cellules cancéreuses épithéliales prostatiques, par le biais de la modulation de l'expression des canaux ioniques impliqués dans le phénomène de Store-Operated Calcium Entry, dont le canal calcique Orai1. Au niveau des cellules épithéliales cancéreuses, nous avons aussi mis en évidence un remodelage de l'expression des canaux ioniques et une résistance à l'apoptose de ces cellules sous l’effet du TCS. Ensuite, nous avons montré dans les cellules stromales de PCa que le TCS induisait une entrée de calcium importante via le canal TRPA1, ce canal étant préférentiellement exprimé dans les cellules stromales de PCa. Par ailleurs, l'augmentation de calcium induite par le TCS est corrélée avec une sécrétion plus importante de VEGF, un facteur mitogène qui pourrait favoriser la croissance des cellules épithéliales ou endothéliales. Ces résultats pourraient permettre d’envisager de nouvelles thérapies ou thérapies complémentaires ciblant les canaux et de mettre en place des mesures préventives dans le traitement des PCa qui prennent en compte l'impact de ces PE. / Environmental factors called "endocrine disruptors (ED)" appear to have a potential role in the development and progression of cancer of the prostate (PCa). It is well established that calcium homeostasis and the activity of ion channels are involved in prostate carcinogenesis and it is possible that these ED promote carcinogenesis by modulating the calcium signalling. In this context, we studied the effect of bisphenol A (BPA) and Triclosan (TCS) on calcium signaling in human PCa cells. We have thus shown that BPA could induce the migration of prostate epithelial cancer cells through the modulation of ion channels expression which are involved in the phenomenon of Store-Operated Calcium Entry, including the calcium channel Orai1. At the level of cancer epithelial cells, we have also highlighted a remodeling of ion channels expression and a resistance to apoptosis of these cells under the influence of TCS. Then, we showed in stromal cells of human PCa that TCS induces an important calcium entry through the TRPA1 channel, this channel being preferentially expressed in stromal cells of PCa. Moreover, the TCS-induced calcium increase is correlated with a greater secretion of VEGF, a mitogenic factor that could promote the growth of epithelial or endothelial cells. These results allow to consider new therapies or complementary therapies targeting ion channels, and/or to implement preventive measures in the treatment of PCa taking into account the impact of these PE.

Triclosan is incorporated in a wide array of medical and consumer products as an antimicrobial agent or preservative. Disposal of these products transport triclosan into wastewater and later into soils and surface waters. Due to incomplete removal of triclosan in wastewater treatment plants, contamination of triclosan in the environment has raised several concerns, including: (i) an aid to the development of cross-resistance to antibiotics, (ii) the toxicity to ecological health, (iii) the formation of chlorodioxins from triclosan and its metabolites. By using 14C-labeled triclosan, 14CO2 was observed in activated sludge samples, suggesting that triclosan was biodegraded. However, little is known about the microorganisms responsible for triclosan biodegradation in activated sludge. The goal of this study is to better understand biodegradation of triclosan in activated sludge. Two specific objectives are: (i) isolating and characterizing triclosan-degrading bacteria from activated sludge, (ii) characterizing the cometabolic degradation of triclosan through an ammonia-oxidizing bacterium Nitrosomonas europaea. A triclosan-degrading strain, KCY1, was successfully isolated from the activated sludge. The strain KCY1 completely degraded triclosan in three days when OD600 was 0.4. Based on 16S rRNA analysis, the strain KCY1 has 97% similarity with Phingomonas or Phingopyxis. Negative results of oxygenase activity assays suggested that other enzymes rather than oxygenases might be responsible for the triclosan biodegradation. Experiments using N. europaea showed that triclosan could be cometabolized. In the presence of inhibitor for ammonia monooxygenase (AMO), N. europaea was unable to degrade triclosan, suggesting that AMO might be responsible for triclosan degradation. Triclosan appeared to competitively inhibit ammonia oxidation by N. europaea. Results of this study showed that triclosan might be effectively biodegraded by triclosan-degrading cultures, strain KCY1 and N. europaea.

Triclosan is incorporated in a wide array of medical and consumer products as an antimicrobial agent or preservative. Disposal of these products transport triclosan into wastewater and later into soils and surface waters. Due to incomplete removal of triclosan in wastewater treatment plants, contamination of triclosan in the environment has raised several concerns, including: (i) an aid to the development of cross-resistance to antibiotics, (ii) the toxicity to ecological health, (iii) the formation of chlorodioxins from triclosan and its metabolites. By using 14C-labeled triclosan, 14CO2 was observed in activated sludge samples, suggesting that triclosan was biodegraded. However, little is known about the microorganisms responsible for triclosan biodegradation in activated sludge. The goal of this study is to better understand biodegradation of triclosan in activated sludge. Two specific objectives are: (i) isolating and characterizing triclosan-degrading bacteria from activated sludge, (ii) characterizing the cometabolic degradation of triclosan through an ammonia-oxidizing bacterium Nitrosomonas europaea. A triclosan-degrading strain, KCY1, was successfully isolated from the activated sludge. The strain KCY1 completely degraded triclosan in three days when OD600 was 0.4. Based on 16S rRNA analysis, the strain KCY1 has 97% similarity with Phingomonas or Phingopyxis. Negative results of oxygenase activity assays suggested that other enzymes rather than oxygenases might be responsible for the triclosan biodegradation. Experiments using N. europaea showed that triclosan could be cometabolized. In the presence of inhibitor for ammonia monooxygenase (AMO), N. europaea was unable to degrade triclosan, suggesting that AMO might be responsible for triclosan degradation. Triclosan appeared to competitively inhibit ammonia oxidation by N. europaea. Results of this study showed that triclosan might be effectively biodegraded by triclosan-degrading cultures, strain KCY1 and N. europaea.

Triclosan, a synthetic antimicrobial agent, is an emerging environmental contaminant. Due to incomplete removal of triclosan by wastewater treatment plants, treated wastewater is one major source of environmental triclosan. Biodegradation of triclosan has been observed in activated sludge and the environment, suggesting that it is possible to develop a cost-effective biotreatment strategy for triclosan removal from wastewater. However, current knowledge on triclosan biodegradation is scarce and limited. To bridge this knowledge gap, this dissertation characterized cultivable triclosan-degrading microorganisms, identified uncultivable triclosan-utilizing bacteria, and elucidated triclosan biodegradation pathways. Furthermore, two treatment strategies were examined to enhance triclosan biodegradation in nitrifying activated sludge (NAS). A wastewater bacterial isolate, Sphingopyxis strain KCY1 (hereafter referred as strain KCY1), can completely degrade triclosan with a stoichiometric release of chloride. This strain can retain its degradation ability toward triclosan when after grown in complex nutrient medium containing triclosan as low as 5 micrograms/L. Based on five identified metabolites, a meta-cleavage pathway was proposed for triclosan biodegradation by strain KCY1. By using [13C12]-triclosan stable isotope probing, eleven uncultured triclosan-utilizing bacteria in a triclosan-degrading microbial consortium were identified. These clones are distributed among alpha-, beta-, or gamma-Proteobacteria, suggesting that triclosan-utilizing bacteria are phylogenetically diverse. None of these clone sequences were similar to known triclosan degraders. Growth substrates affected the triclosan degradation potential of four selected oxygenase-expressing bacteria. Biphenyl-grown Burkholderia xenovorans LB400 and propane-grown Rhodococcus ruber ENV425 cannot degrade triclosan. On the other hand, propane- and 2-propanol-grown Mycobacterium vaccae JOB5 can degrade triclosan completely. Due to product toxicity, finite transformation capacities for triclosan were observed for Rhodococcus jostii RHA1 grown on biphenyl, propane, and LB medium with dicyclopropylketone (alkane monooxygenase inducer). Four chlorinated metabolites were detected during triclosan degradation by biphenyl-grown RHA1 and a meta-cleavage pathway was proposed. Complete triclosan (5 mg/L) degradation was observed within 96 hrs in NAS receiving ammonia amendment (0 to 75 mg/L of NH4-N). The fastest triclosan degradation was observed in the NAS exhibiting the highest amount of ammonia. When ammonia oxidation was active in NAS, the amendment of strain KCY1 did not further enhance triclosan removal. Overall, the results suggested that triclosan biodegradation can be enhanced by increasing the activity of ammonia oxidation in NAS.

This study looked at effects of organic solvents dimethylsulfoxide, dimethylformamide and acetone at 0.01%, 0.05% and 0.1% concentration on germination and seedling development wetland plants. Even at 0.01% level, all solvents affected some aspect of seed germination or seedling growth. Acetone at 0.01% was least toxic. Root morphological characteristics were most sensitive compared to shoot morphological characteristics. This study also looked at bioconcentration patterns of antimicrobial compounds triclosan, triclocarban and methyl-triclosan in wetland plants exposed to Denton Municipal Waste Water Treatment Plant effluent. Bioconcentration patterns of antimicrobial compounds varied among species within groups as well as within organs of species. The highest triclocarban, triclosan and methyltriclosan concentration were in shoot of N. guadalupensis, root of N. lutea and in shoots of P. nodous respectively.

Triclosan (TCS) is an antimicrobial compound found in several types of common household products. After being washed down the drain, TCS will then end up in the local watershed. Although numerous studies have been conducted to evaluate the fate and effects of TCS in aquatic environments, there have been no studies evaluating the role arbuscular mycorrhizal fungi (AM) play in a plants response to TCS exposure. Three species of wetland plants native North Texas were inoculated with AM spores and exposed to 0, 0.4 g/L and 4.0 g/L TCS concentrations. Root morphology of E. prostrata and S. herbacea showed AM and exposure responses. S. herbacea produced the greatest amounts biomass and TCS bioaccumulation, in all but one treatment. It also displayed opposing results to E. prostrata in measures of root length, root surface area, relative root mass, relative shoot mass and shoot:root ratio. TCS root tissue concentrations increased with increased exposures for both E. prostrata and S. herbacea. Even though E. prostrata had the lowest levels in each measure of biomass production, it had the highest amount of root TCS bioaccumulation in the AM inoculated 4.0 g/L treatment. H. laevis was between the other two species in terms of biomass production, and did not demonstrate any exposure or inoculation effects in morphology or TCS accumulation. Overall, no clear patterns were detected, which highlights the fact that further study is required to completely understand the effects compounds like TCS can have on plant community structure, and ultimately ecosystem function.

In the last decade emerging contaminants research has intensified in a bid to answer questions about fate, transport, and effects as these chemicals as they get released into the environment. The chemicals of interest were the antimicrobials; triclocarban (TCC) and triclosan (TCS), and a metabolite of triclosan, methyl triclosan (MTCS). This research was designed to answer the question: what is the fate of these chemicals once they are released from the waste water treatment plant into receiving streams. Three different assessment methods; field monitoring, in-situ experiments, and laboratory studies were used to answer the overall question. TCS, TCC, and MTCS levels were measured in surface water, sediment and the Asiatic clam Corbicula fluminea. Field studies were conducted using four sites at Pecan Creek, Denton TX. Levels of all three chemicals in clams were up to fives orders of magnitude the water concentrations but an order of magnitude lower than in sediment. Highest sediment levels of chemicals were measured in samples from the mouth of Pecan Creek (highest organic matter). TCC was the most and TCS was the least accumulated chemicals. In-situ and lab studies both indicated that uptake of these chemicals into the clams was very rapid and measurable within 24hours of exposure. The after clams were transferred into clean water most of the compounds were depurated within 14 days.

Le paludisme est la plus importante infection parasitaire dans le monde, menaçant environ 40% de la population humaine. Dans les dernières années c'est devenu un problème de santé publique majeur en raison de l'augmentation des parasites résistants aux traitements actuels. Certains complexes NHC-or(I) présentent des activités antipaludiques, et sont une alternative très prometteuse dans le traitement du paludisme en raison de leur potentiel inhibiteur de la thiorédoxine réductase (TrxR) qui joue un rôle majeur dans la chaîne respiratoire mitochondriale (une des deux voies actives à l'état de quiescence des parasites résistants). Dans ce travail de thèse, un panel de complexes médicament-NHC-or(I) a été synthétisé et caractérisé. Le premier groupe de molécules concerne une famille de complexes cationiques bis-NHC-or(I) et de complexes neutres mono-NHC-or(I) fonctionnalisés avec substituents aliphatiques ou aromatiques. Le groupe comprend trois séries. Les trois séries ont été testées contre la souche sensible de F32-TEM de P. falciparum présentant des activités élevées, avec des valeurs d'IC50 de l'orde du nM. Le deuxième groupe concerne une série de complexes cationiques bis-NHC-or(I) fonctionnalisés avec des substituants aliphatiques ou aromatiques comprenant un groupement triclosan relié par un connecteur aliphatique. Le triclosan inhibe la voie de synthèse des acides gras, qui reste également active chez les parasites résistants. Ces complexes ont été testés contre P. falciparum, montrant des activités élevées avec des valeurs IC50 dans la gamme du nM. Les ligands de cette série et leurs complexes respectifs ont également été testés contre L. infantum, l'un des parasites provoquant la leishmaniose, et se sont révélés très efficaces sous les formes amastigote et promastigote, avec des valeurs d'IC50 dans le bas µM. / Malaria is the most important parasitic infection in people, threatening around 40% of the human population. In the last years it has become a bigger public health concern because of the augmentation of malaria parasites resistant to artemisinin and its derivatives. Some NHC-gold(I) complexes show antimalarial activities, being a very promising alternative in malaria treatment because of their potential to inhibit thioredoxin reductase (TrxR) that plays a major role in mitochondrial respiratory chain (one of the two pathways that remains active in the quiescent state of the resistant parasites). In this work of thesis a panel of drug-NHC-gold(I) complexes including artemisinin and triclosan moieties has been synthesized and characterized with the objective of developing hybrid molecules with a dual mode of action able to overcome plasmodium resistance to artemisinin and its derivatives. The first group of molecules concerns a family of aliphatic or aromatic-functionalized cationic bis-NHC-gold(I) and neutral mono-NHC-gold(I) complexes with an artemisinin moiety connected through an aliphatic linker. The group includes three series depending on the length of the aliphatic linker (C3, C4, and C5). The three series have been tested against the sensible F32-TEM strain of P. falciparum showing high activities with IC50 values in the nM range. The second group concerns a series of aliphatic or aromatic-functionalized bis-NHC-gold(I) complexes with an triclosan moiety connected through an aliphatic linker. Triclosan inhibits the fatty acid synthesis pathway, which also remains active in the quiescent state on resistant parasites. These complexes were tested against P. falciparum showing, high activities with IC50 values in the nM range. The ligands of this series and their respective complexes have been also tested against one of the leishmaniosis causing parasites, L. infantum, being very effective in both, amastigote and promastigote forms, with IC50 values in the low µM range.

A confecção da estrutura 3D do óxido de grafeno/L-cisteína foi obtida por meio da sequência de etapas descritas a seguir. Primeiramente, o óxido de grafeno foi sintetizado por meio da oxidação do grafite, utilizando permanganato de potássio e ácido sulfúrico, seguido pela esfoliação em ultrassom. Depois, a preparação do material de grafeno 3D ocorreu por auto-montagem e redução simultânea do óxido de grafeno, usando L-cisteína como agente de modelização e redução. A caracterização do material preparado deu-se por: microscopia eletrônica de varredura (MEV), análise por adsorção de nitrogênio (BET), espectroscopia na região do infravermelho com transformada de Fourier (FT-IR) e difração de raios-X (DRX). O método de análise empregado foi à cromatografia em fase líquida de alta eficiência com detector UV-Visível (HPLC-UV). Este foi desenvolvido e validado para determinação do triclosan em amostras aquosas. As figuras de mérito avaliadas foram: limite de detecção (LD) e quantificação (LQ), seletividade, linearidade e recuperação. O percentual de triclosan adsorvido em 40 mg de óxido de grafeno/L-cisteína mostrou-se elevado para soluções de triclosan em solvente, 100%; no entanto, para amostras de água de superfície fortificadas com triclosan, foi de 67,8%. A dessorção do triclosan foi praticamente completa em todas as soluções testadas, variando de 94,2% a 98,1%. A reutilização de óxido de grafeno/L-cisteína mostrou-se promissora, uma vez que apresentou adsorção completa mesmo após três ciclos consecutivos de percolação de triclosan em solvente / The construction of the 3D structure of the graphene oxide/L-cysteine was obtained by the sequence of steps described below. Firstly, graphene oxide was synthesized by oxidation of graphite using potassium permanganate and sulfuric acid, followed by ultrasonic esfoliation. Then, the preparation of 3D graphene material occurred by self-assembly and simultaneous reduction of graphene oxide, using L-cysteine as a modeling and reduction agent. The characterization of the prepared material was given by: scanning electron microscopy (SEM), nitrogen adsorption analysis (BET), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The analytical method was high performance liquid phase chromatography with UV-Visible detector (HPLC-UV). This was developed and validated for the triclosan determination. The figures of merit evaluated were: limit of detection (LOD) and quantification (LOQ), selectivity, linearity and recovery. The percentage of trichlosan adsorbed in 40 mg of graphene oxide/L-cysteine was shown to be high for solutions of triclosan in solvent, 100%; however, for surface water samples fortified with triclosan, it was 67.8%. Desiccation of triclosan was practically complete in all tested solutions, varying from 94.2% to 98.1%. The reuse of graphene oxide/L-cysteine had shown promising, since it presented complete adsorption even after three consecutive cycles of percolation of triclosan in solvent.