Dissertations / Theses on the topic 'Bacterial resistance'
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Chung, Whasun Oh. "Macrolide resistance and its linkage to tetracycline resistance /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/9279.
Full textPowell, James Patrick. "Antibiotic Diversity and Bacterial Resistance." Available to users online at:, 2007. http://hdl.handle.net/10156/1303.
Full textMesser, Janet Mariam. "Bacterial resistance ot glycopeptide antibiotics." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239488.
Full textBrown, Keith L. "Heat resistance of bacterial spores." Thesis, University of Nottingham, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317036.
Full textSütterlin, Susanne. "Aspects of Bacterial Resistance to Silver." Doctoral thesis, Uppsala universitet, Klinisk mikrobiologi och infektionsmedicin, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-247472.
Full textCrossland, Richard J. "Mathematical modelling of bacterial mercury resistance." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/30521/.
Full textLeszcynski, Robert A. "Determination of the Relationship Between Bacterial Coculturing, Antibiotic Resistance and Bacterial Growth." University of Dayton / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1591787505690696.
Full textI, D'Agostino. "Polyalkylguanidines: new weapons to tackle bacterial resistance." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1070884.
Full textCousin, Sydney Louis. "Macrolide resistance in Neisseria gonorrhoeae /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/5078.
Full textNilsson, Annika. "Bacterial adaptation to novel selection pressures /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-192-X/.
Full textGiske, Christian G. "Carbapenem resistance in Pseudomonas aeruginosa /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-080-0/.
Full textWood, Ryan. "Bacteria in Blood: Optimized Recovery of Bacterial DNA for Rapid Identification." BYU ScholarsArchive, 2020. https://scholarsarchive.byu.edu/etd/8147.
Full textReyes, Nikolle Susanne. "Marine bacterial isolates utilize unique mercury resistance mechanisms." Thesis, Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/25416.
Full textGao, Feng. "Synthesis of aminoglycoside derivatives to combat bacterial resistance." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=18273.
Full textLes aminoglycosides sont des antibiotiques à large spectre. Ils agissent en se fixant à l'ARN ribosomal 16S des bactéries et perturbent la synthèse protéique. L'extension rapide du phénomène de résistance aux aminoglycosides menace cependant leur efficacité. Parmi les différents mécanismes de résistance aux aminoglycosides, le plus important est la production d'enzymes inactivant l'antibiotique. Trois types d'enzymes impliquées dans ce mécanisme ont été identifiés, à savoir les aminoglycoside-N-acétyltransférases (AACs), les aminoglycoside-O-phosphoryltransférases (APHs) et les aminoglycoside-O-nucléotidyltransférases (ANTs). Deux approches peuvent être envisagées pour combattre ou contourner le phénomène de résistance. La première consiste à créer de nouveaux antibiotiques en modifiant des antibiotiques existant. L’autre implique le développement d'inhibiteurs capables de bloquer la résistance. Une nouvelle méthodologie pour la dérivatisation régio- et chimio-sélective d'aminoglycosides non protégés à la position N-6' a été développée. Cette méthode a ensuite été appliquée à la synthèse d'une série de bisubstrats aminoglycoside-coenzyme A. Ces analogues se sont avérés être de puissants inhibiteurs (resistance d'inhibition de l'ordre de la nanomole) de l'enzyme aminoglycoside 6'-N acétyltransférase Ii (AAC(6')-Ii), impliquée dans la résistance à de nombreux antibiotiques aminoglycosides. Plus particulièrement, ces molécules ont pu être co-cristallisées avec AAC(6')-Ii par nos collaborateurs, qui n'étaient à ce jour jamais parvenus à cristalliser cette enzyme avec un aminoglycoside. Les structures 3D ainsi obtenues ont permis d'obtenir de précieuses informations sur le site de fixation des aminoglycosides. Une deuxième génération d’inhibiteurs de l'AAC(6')-Ii a ensuite été synthétisée. Elle consistait en une série d'analogues tronqués de la première génération d'inhibiteurs. Ces ana
Lloyd, Bryony Helen. "Bacterial resistance to tellurite and other metal ions." Thesis, University of Liverpool, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333673.
Full textLindsay, Sharon. "Population antibiotic-resistance : a study of bacterial persistence." Thesis, University of Manchester, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528276.
Full textIvanova, Aleksandra Asenova. "Nanomaterials for controlling bacterial pathogens and resistance occurrence." Doctoral thesis, Universitat Politècnica de Catalunya, 2022. http://hdl.handle.net/10803/673983.
Full textLas enfermedades infecciosas son la principal causa de muerte en todo el mundo. Mientras que la resistencia a los antimicrobianos es una preocupación importante para la salud pública. Durante el establecimiento de la infección los patógenos bacterianos se comunican mediante la expresión de moléculas de señalización controladas mediante un fenómeno llamado detección de quórum (QS). Como resultado, las bacterias producen factores de virulencia y forman biopelículas resistentes que causan infecciones persistentes. Las infecciones causadas por patógenos resistentes a los antibióticos se asocian con una alta morbilidad mortalidad y una enorme carga económica. A diferencia de la disminución en las últimas tres décadas del número de nuevos medicamentos antimicrobianos comercializados el número de cepas bacterianas resistentes a los antibióticos aumenta constantemente. Por lo tanto existe la necesidad urgente de desarrollar estrategias alternativas para manejar infecciones diflciles de tratar. Esta tesis tiene como objeto de trabajo la ingenieria de materiales y recubrimientos avanzados nano estructurados para controlar la patogénesis bacteriana y la aparición de resistencias. Para lograrlo se combina polímeros anti biopelícula, enzimas anti infecciosas y compuestos inorgánicos como estrategias alternativas a los antibióticos convencionales. La nanoforma puede proporcionar una interacción mejorada con las membranas celulares bacterianas y una penetración más fácil en las biopelículas, aumentando la eficacia antimicrobiana en dosis más bajas al mismo tiempo que previene el desarrollo de resistencia antimicrobiana. Además las fracciones de orientación especificas aumentan la interacción del nano material con los patógenos evitando la aparición de resistencia al fármaco y la citotoxicidad.La primera parte de la tesis describe la funcionalización de nano partículas (NP) biológicamente inertes con aminocelulosa antimicrobiana (AM) perturbadora de la membrana y ácido hialurónico (HA) biocompatible en forma de LbL para la eliminación de patógenos médicamente relevantes. Las nanoentidades generadas demuestran un alto potencial para inhibir la formación de biopelículas sin afectar la viabilidad en las células humanas. Además, la técnica L.bL se aplica para decorar nanoplantillas de plata (Ag) antimicrobianas,pero potencialmente tóxicas con PNt biocompatible y acilasa de extinción de quórum (QQ) para obtener nanomateriales antibacterianos y anti biopelícula seguros. La deposición de acilasa y PNt en el núcleo de Ag interfiere con la señalización de QS y la patogénesis bacteriana y mejora la interacción de las NP con la membrana bacteriana. La integración de un triple mecanismo de acción en las nanoentidades híbridas da como resultado la erradicación completa de bacterias y biopelículas y una mejor biocompatibilidad de los AgNP. La tesis también describe el desarrollo de nanocápsulas dirigidas (NC) para la eliminación selectiva de Staphylococcus aureus. En este trabajo se aplica la tecnología de nanoencapsulación de autoensamblaje que utiliza la proteína Zeína biocompatible y biodegradable para la generación de NC de Zelna cargadas con aceite esencial de orégano bactericida.Un anticuerpo dirigido específicamente a S.aureus se injerta covalentemente en la superficie de las NC. Las NC dirigidos obtenidos demuestran selectividad antibacteriana en un inóculo bacteriano mixto.y la eficacia del tratamiento se valida en un modelo de cocultivo in vitro de bacterias y células de mamíferos.Finalmente, se emplea un proceso de ultrasonoqufmica de alta intensidad. Para la ingeniería de un recubrimiento antibacterlano/anti biopelícula duradero en catéteres urinarios. La deposición de NP de Óxido de Zinc y enzima amilasa que degrada la matriz.mejora la adhesión de las NP en el material de silicona evitando su colonización bacteriana y la formación de biopeliculas in vitro
Polímers i biopolímers
Ouma, Christine. "REDUCING BACTERIAL RESISTANCE THROUGH BETTER ANTIBIOTIC PRESCRIPTION PRACTICES." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1580.
Full textFrost, Isabel. "The evolution of antibiotic resistance in bacterial colonies." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:8dc07d49-0eb4-42fd-9a8e-ac3984eb587c.
Full textGriffith, James T. "The Influence of Antimicrobial use on Bacterial Resistance." ScholarWorks, 1992. https://scholarworks.waldenu.edu/dissertations/1395.
Full textRiscado, Andreia Catarina Morgado. "Estudo das (multi)resistências bacterianas em clínica de animais de companhia." Master's thesis, Universidade de Évora, 2020. http://hdl.handle.net/10174/27834.
Full textGuest, Kerry Teresa. "Bacterial resistance to oxidising biocides : an assessment of resistance mechanisms and method development." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/94443/.
Full textIvanova, Kristina Dimitrova. "Nanostructured coatings for controlling bacterial biofilms and antibiotic resistance." Doctoral thesis, Universitat Politècnica de Catalunya, 2017. http://hdl.handle.net/10803/405631.
Full textLa rápida aparición de bacterias resistentes a fármacos es uno de los problemas más graves del sistema sanitario convirtiéndose en un gran reto encontrar nuevos antibióticos. Para superar la acción de los antibióticos, las bacterias utilizan diferentes mecanismos de resistencia incluyendo la formación de biopelículas. Las biopelículas son comunidades complejas de células bacterianas unidas por una matriz polimérica comúnmente encontradas en dispositivos médicos invasivos como los catéteres urinarios. Cuando los patógenos adoptan este modo de crecimiento en superficies, evitan eficazmente las defensas inmunitarias y el efecto de los antibióticos, causando infecciones. Esta tesis se centra en el desarrollo de nuevos materiales y recubrimientos nanoestructurados para el control de biopelículas bacterianas y la reducción de su resistencia a antibióticos. Por lo tanto, las enzimas acilasa y amilasa, capaces de degradar los componentes necesarios de las bacterias para formar biopelículas, se combinaron de forma innovadora en nanorecubrimientos híbridos para intervenir en el crecimiento de las biopelículas en dispositivos médicos permanentes. Además, la transformación de agentes antimicrobianos a forma "nano" se utilizó para mejorar su eficacia antibacteriana y superarlos mecanismos de resistencia a fármacos de las bacterias. Estas estrategias ofrecen nuevas perspectivas para el tratamiento de las infecciones relacionadas con biopelículas, limitando la selección y propagación de la resistencia bacteriana. La primera parte de la tesis describe la generación de recubrimientos multicapa de enzimas capaces de interferir con el sistema de comunicación bacteriana, denominado quórum sensing (QS) y prevenir la formación de biopelículas en el superficie de los catéteres urinarios. Esto se consiguió por deposición alternada de acilasa, cargada negativamente, y polietilenimina, cargada de manera opuesta, en la forma de capa a capa (LbL). Los catéteres recubiertos con acilasa inhibieron el proceso QS de bacterias Gram-negativas y redujeron significativamente el crecimiento de biopelículas en los catéteres urinarios en condiciones que imitaban la situación real en pacientes cateterizados. Adicionalmente, la acilasa se combinó con la enzima amilasa en recubrimientos híbridos capaces de interferir con las señales de comunicación entre bacterias y la integridad de la matriz de la biopelícula. El ensamblaje de las dos enzimas en recubrimientos híbridos dio lugar a una inhibición de la formación de biopelículas más fuerte en función de la localización de la acilasa o de la amilasa en la multicapa. Nanorecubrimientos con acilasa en la capa más externa redujo la formación de biopelículas en catéteres de silicona in vitro y en un modelo animal in vivo. La tesis también muestra la eficacia de nanomateriales para el control de biopelículas bacterianas. Las nanoesferas (NSs) antibacterianas, que contienen en su estructura multicapas ensambladas que se liberan bajo demanda, fueron depositados sobre silicona. Aminocelulosa (AC) se transformó primero en NSs obteniendo una mejor actividad bactericida y luego se combinó con ácido hialurónico para construir capas sensibles a las bacterias. Cuando se ponen en contacto con bacterias, estas capas se desmontan gradualmente inhibiendo las formas planctónicas y biopelículas. Los mismos ACNS también se inmovilizaron sobre silicona usando epoxi-amina. Las NSs intactas fueron capaces de inhibir el crecimiento de la biopelícula, lo que demuestra el potencial de la reacción de epoxi-amina para la generación de recubrimientos estables en dispositivos médicos de silicona. Finalmente, la nanotransformación de la penicilina G se utilizó como otra estrategia para aumentar la actividad del antibiótico hacia bacterias. Se demostró la a penetración efectiva de las partículas dentro de membrananas biomimeticas sugiera que las partículas alcanzan el espacio periplásmico en las bacterias y ejercen su actividad bactericida.
Purewal, Amarjit S. "Bacterial genetic determinants specifying resistance to cationic antimicrobial agents." Thesis, University of Hull, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253168.
Full textBendall, J. B. "Bacterial resistance to antimicrobial agents in geriatric medical wards." Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381441.
Full textOsborn, Andrew Mark. "Evolutionary analysis of bacterial mercury resistance in natural environments." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262489.
Full textKnapp, Laura. "Bacterial resistance to biocides : development of a predictive protocol." Thesis, Cardiff University, 2014. http://orca.cf.ac.uk/60862/.
Full textPietsch, Franziska. "Evolution of Antibiotic Resistance." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-265018.
Full textHopkins, J. M. "Mechanisms of cefotaxime resistance in Enterobacter SPP." Thesis, University of Nottingham, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384328.
Full textSimmons, Carla Stull. "Influence of copper on resistance of Lumbricus terrestris to bacterial challenge." Thesis, University of North Texas, 2000. https://digital.library.unt.edu/ark:/67531/metadc2602/.
Full textPränting, Maria. "Bacterial Resistance to Antimicrobial Peptides : Rates, Mechanisms and Fitness Effects." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-130168.
Full textVandal, Omar Haider. "Mycobacterium tuberculosis and the macrophage : host defenses and bacterial resistance /." Access full-text from WCMC:, 2008. http://proquest.umi.com/pqdweb?did=1428864551&sid=6&Fmt=2&clientId=8424&RQT=309&VName=PQD.
Full textSyed, Mohamed Ami Fazlin. "Pharmacokinetic and Pharmacodynamic Modeling of Antibiotics and Bacterial Drug Resistance." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-188306.
Full textMiller, Keith. "Role of bacterial hypermutators in the evolution of antimicrobial resistance." Thesis, University of Leeds, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275754.
Full textLofton, Tomenius Hava. "Mechanisms and Biological Costs of Bacterial Resistance to Antimicrobial Peptides." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-284119.
Full textJayawardana, Malini Anudya. "Genetic Mapping of Resistance to Bacterial Leaf Streak in Triticale." Thesis, North Dakota State University, 2017. https://hdl.handle.net/10365/28661.
Full textLee, Miseon. "THE DISCOVERY OF NOVEL MACROLIDE ANTIBIOTICS THAT ADDRESS BACTERIAL RESISTANCE." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/436439.
Full textPh.D.
Bacterial resistance is a formidable 21st-century global public health threat. If left unaddressed, we risk moving toward a “post-antibiotic era.” While resistance is a natural consequence of antibiotic use, the rate at which pathogenic bacteria have evaded multiple classes of drugs has markedly outpaced the introduction of new ones. New antibiotics are desperately needed to fill this void. Macrolides are one of the safest and most effective drug classes in medicine; however, resistance has compromised efficacy. To date, three generations have been developed with only the lattermost targeting bacterial resistance. Single next-generation macrolides will not keep pace with the inevitable onset of resistance; thus, there is a critical need to greatly accelerate the procurement of multiple future-generation antibiotics to tackle both current and future resistance mechanisms. My research is to meet this need by designing, synthesizing, and evaluating a novel, future-generation macrolide antibiotics that will serve as an armamentarium to be individually deployed on demand. In the previous research in Andrade group, we synthesized and evaluated various desmethyl ketolide analogs. The fact that 4-desmethyl telithromycin was fourfold less potent than telithromycin against A2058G mutants indicated replacing the 4-Me with hydrogen (i.e., desmethylation) to avoid a steric clash with the 2-amino group of G2058 was insufficient in rescuing bioactivity. Guided by MD simulation, we concluded a logical, superior alternative strategy was the replacement of the 4-Me group with one possessing a smaller vdW radius and capable of establishing favorable interactions with both wild-type and A2058G mutant ribosomes. Specifically, we reasoned that 4-fluoro solithromycin would be ideal candidate. The hypothesis was that the 4-fluoro moiety would engage in dipole-dipole interactions (C-F---H) with the exocyclic 2-amino group of guanine, which is based on accumulated evidence that strategic placement of organofluorine can strongly impact potency, selectivity, and physicochemical properties. In addition, the axially disposed of 4-fluorine would provide conformational stabilization from a gauche effect with the vicinal O5 group. The novel synthetic routes to unexplored desosamine analogs at the C3’-amino substituent to the macrolide antibiotic would play a role in bioactivity and resistance. Hofmann reaction was employed to execute the same 2,3-epoxide ring opening method without removing desosamine and re-glycosylating. This markedly reduces the steps, time, and cost involved in preparing novel desosamine-modified analogs. Significantly, this route enables the first synthesis of N,N’-disubstituted desosamine analogs from an epoxide, which was utilized to prepare novel analogs of clarithromycin. The application of in situ click chemistry toward the discovery of novel macrolide antibiotics first required the synthesis of suitable azide and aryl alkyne reactants. Alkyne partners were procured by commercial vendors or chemical synthesis. We targeted two logical, validated positions to tether the side chains, specifically N11 on the macrolactone and N3’ of desosamine. The first (N11) has been the most utilized. Moreover, extensive structure-activity relationships have revealed a four-carbon tether is ideal. Based on the solithromycin−E.coli X-ray structure, I designed, synthesized, and evaluated dehydro solithromycin, which possesses an (E)-alkene in the side-chain. The use of an unsaturated side chain would conformationally preorganize the bi-aryl side chain in order to pay the entropic penalty and thus favorably contribute to the overall binding. An insightful observation made from MD simulationed ribosomes bound with to solithromycin revealed that the interaction of the side-chain includes H-binding as well as π-stacking. The hypothesis was that employing tethered side-chains bearing motifs that maximize H-bonding and π-stacking would be superior antibiotics for treating resistant bacterial strains bearing erm¬-mediated N6 methyl and dimethylated ribosomes. To test this hypothesis, we developed various analogs with different alkynes by introducing different functional groups at the 3 and 5 positions on the aromatic ring. Another desosamine sugar modification is bis-azide. To date, the use of a two side chain strategy has not been reported. To access the requisite bis-azides, we employed a tactic the oxidative demethylation and alkylation of desosamine to afford bis-click solithromycin analogs.
Temple University--Theses
Jobling, M. G. "Physical and genetic analysis of heavy metal resistance plasmids." Thesis, University of Liverpool, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372683.
Full textHart, Mark Christopher. "Mercury resistance genes in a natural Bacillus population." Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366004.
Full textLiu, Xiulan. "Characterisation of antibiotic resistance gene clusters and their mobility within a collection of multi-drug resistant Salmonella spp." School of Biological Sciences - Faculty of Science, 2009. http://ro.uow.edu.au/theses/3043.
Full textErlandsson, Marcus. "Surveillance of Antibiotic Consumption and Antibiotic Resistance in Swedish Intensive Care Units." Doctoral thesis, Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1019s.pdf.
Full textPaulander, Wilhelm. "Mechanisms of adaptation to the fitness cost of antibiotic resistance /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-149-4/.
Full textDavies, Sarah Elisabeth. "Development of antimicrobial resistance in Acinetobacter spp and methicillin-resistant Staphylococcus aureus." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4388.
Full textLewandowski, Eric Michael. "Structure Based Drug Design Targeting Bacterial Antibiotic Resistance and Alzheimer's Disease." Scholar Commons, 2015. http://scholarcommons.usf.edu/etd/5982.
Full textOliver, Kerry M. "The role of pea aphid bacterial symbionts in resistance to parasitism." Diss., Tucson, Arizona : University of Arizona, 2005. http://etd.library.arizona.edu/etd/GetFileServlet?file=file:///data1/pdf/etd/azu%5Fetd%5F1031%5F1%5Fm.pdf&type=application/pdf.
Full textYan, Xuxu. "Synthesis and biological study of aminoglycoside derivatives to overcome bacterial resistance." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96824.
Full textLes aminoglycosides sont des antibiotiques à large spectre qui ciblent le site A de l'ARN ribosomique 16S dans la bactérie. Leur usage, par contre, est de plus en plus menacé à cause de l'étendue rapide de la résistance contre les aminoglycosides. La classe d'enzyme aminoglycoside-6′-N-acétyltransférases (AAC(6′)) est l'un des détermiants de résistance le plus commun. Ces enzymes utilisent acétylcoenzyme A (AcCoA) pour acétyler plusieurs aminoglycosides à la position 6′-NH2, ce qui diminue leur affinité pour l'ARN et la résistance en résulte. Une des stratégies privilégiée par notre groupe de recherche pour combattre la résistance aux aminoglycosides est décrite au Chapître 2. Elle consiste à développer des inhibiteurs contre AAC(6′). La première génération d'inhibiteurs, des bisubstrats de type aminoglycoside-CoA, a démontré une inhibition compétitive nanomolaire in vitro. Quoiqu'ils fussent utiles comme éléments de recherche structurale et mechanistique, ils ne démontrent aucune activité biologique. L'étude subséquente d'analogues de bisubstrats raccourcis a permis d'établir des relations structure-activité et a mené à la découverte d'une seconde génération d'inhibiteurs, incluant une molécule avant la capacité de bloquer la résistance aux aminoglycosides dans les cellules bactériennes exprimant l'AAC(6′)-Ii. Pour améliorer l'efficacité de ce composé, nous avons synthétisé une troisième génération d'inhibiteurs dont l'ester a été remplacé par divers groupements amide. L'hypothèse était que l'amide serait plus stable, menant à des composés plus stables et plus efficace, biologiquement parlant. À notre surprise, ces modifications ont diminué de façon significative l'interaction entre les inhibiteurs et AAC(6′)-Ii. Le troisième chapître de cette thèse explore une autre stratégie pour contrer la résistance envers les aminoglycosides. Elle vise à créer des agents antibactériens actifs contre les bactéries résistantes. Une série de dérivés de néamine acylés à la position 6′-N ont été envisagés afin de retenir l'habileté de l'amine 6′ à faire un lien hydrogène avec l'ARN tout en perturbant l'adhérance envers l'AAC(6′). Certains composés ont démontré des propriétés antibactériennes modérées dans les cellules mais sans potentiel clinique. Enfin, notre troisième approche vise à créer des pro-médicaments possédant à la fois la capacité de contrer la résistance ainsi que des propriétés antibactériennes. Notre but était de développer des dérivés d'aminoglycoside qui seraient transformés en analogues de bisubstrats par les enzymes bactériennes impliquées dans la biosynthèse de CoA. Les bisubstrats résultant pourraient non seulement bloquer la résistance en inhibitant l'enzyme AAC(6′), mais aussi avoir des propriétés antibactériennes en affectant la biosynthèse des acides gras. Une série de ces dérivés d'aminoglycosides a été synthétisée et aucun produit ne montre d'activité antibacterienne. Par contre, des résultats préliminaires suggèrent que même si ces molecules n'inhibitent pas l'enzyme AAC(6') purifiée, elles possèdent l'habileté d'augmenter l'action des aminoglycosides dans les bactéries résistantes. Selon nos connaissances, il s'agit des premiers pro-médicaments capablent de bloquer la resistance aux aminoglycosides dans les cellules.
De, Pieri Lucrezia A. "A study of light scattering and heat resistance of bacterial spores." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293146.
Full textWong, Ruth. "Structure and function of multidrug efflux systems in bacterial antibiotic resistance." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612755.
Full textBiesecker, Steven. "THE ROLE OF BACTERIAL AMYLOID FIBRILS IN ESCHERICHIA COLI COMPLEMENT RESISTANCE." Master's thesis, Temple University Libraries, 2012. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/174200.
Full textM.S.
Strains of Escherichia coli may exist as a beneficial human commensal or a pathogen capable of causing morbidity and mortality. Of the E. coli which causes human disease, many strains which cause bacteremia have been identified as possessing virulence factors which make them more resistant to the complement system. The bacterial amyloid fibril, curli, functions in bacterial adherence and the formation of biofilm. Curli-producing parental and curli-deficient mutant E. coli was compared in its survival to human complement, using in vitro serum sensitivity assays. Results showed an increase in the survival of curli-producing E. coli, which suggested that curli defends against complement killing. An in vivo murine model of E. coli-induced sepsis demonstrated that curli-producing bacteria also survived significantly better in the blood of mice. Immunostaining and flow cytometry was done to determine if parental and mutant strains of E. coli differentially bind to complement components C1q and C3. Results demonstrated that curli increases binding of C1q, but does not affect C3 binding. Blocking the classical pathway suggested that, in these assays, the classical pathway was the major contributor to complement activation and curli inhibits its activity. In addition, blocking the alternative pathway supported that the classical pathway was the main mechanism for complement activation and suggested that curli is not involved in protecting E. coli against alternative pathway activation. Results of this study conclude that curli defends E. coli against complement killing via inhibition of the classical complement pathway.
Temple University--Theses
May, Megan Katherine. "Characterizing bacterial antibiotic resistance, prevalence, and persistence in the marine environment." Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122524.
Full textCataloged from PDF version of thesis.
Includes bibliographical references.
Antibiotics are naturally occurring chemicals in bacteria that were recently discovered and utilized by humans. Despite a relatively short time of use, anthropogenic use of antibiotics has increased natural levels of antibiotic resistance, which has caused a looming antibiotic resistance crisis, where antibiotics may not work. Understanding resistance patterns is critical to allow for continued therapeutic use of antibiotics. While resistance is often thought of in hospitals, antibiotics and antibiotic resistance genes from human activity are disposed of into nature where they are able to interact with naturally occurring antibiotics and resistance. In this dissertation, I examine the ocean as an understudied region of the environment for antibiotic resistance. The ocean represents an area of human activity with recreation and food consumption and it is an enormous region of the planet that is affected by both land and sea activities.
In Chapter 2, I explore the policies that have contributed to the antibiotic resistance crisis. I offer explanations of market and political failures that contributed to the situation, areas for growth in terms of assessing scientific knowledge, and finally, recommendations for mitigating antibiotic resistance. In Chapters 3 and 4, I collected individual bacterial cultures from Cape Cod, MA beaches to assess the phenotypic response to antibiotic resistance. I show that 73% of Vibrio-like bacteria and 95% of heterotrophic bacteria (both groups operationally defined) are resistant to at least one antibiotic. These results indicate that antibiotic resistance is prevalent and persistent on beaches over both spatial and temporal scales. In Chapter 5, I used metagenomics to assess the abundance and types of resistance genes at coastal impacted Massachusetts sites. I found that, even in sites that seem distinct in terms of anthropogenic impact, prevalence of resistance remained the same.
Finally, in Appendix A, I examined part of the TARA Ocean dataset for prevalence of antibiotic resistance genes across the world's ocean. Here, I found that there are distinctions between different ocean biomes based upon antibiotic, metal, and mobile genetic elements. This dissertation has increased the understanding of temporal and spatial dynamics of antibiotic resistance in the coastal and open ocean.
"This work has be funded by the National Science Foundation Graduate Research Fellowship under Grant No. 1122374 and a Martin Fellows for Sustainability Fellowship (both to MKM). Grants from Woods Hole Oceanographic Institution from the Coastal Ocean Institute, Grassle Family Foundation, Hill Family Foundation, and Biology Department also supported this work"--Page 6
by Megan Katherine May.
Ph. D.
Ph.D. Joint Program in Oceanography/Applied Ocean Science and Engineering (Massachusetts Institute of Technology, Department of Biology; and the Woods Hole Oceanographic Institution)