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1
Chastel, Michaël Foucras Gilles. "Épidémiologie de la paratuberculose des ruminants conséquences sur les mesures de contrôle et de prévention /." [S.l.] : [s.n.], 2008. http://oatao.univ-toulouse.fr/2081/1/debouch_2081.pdf.
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Mathie, Heather. "Early macrophage response to Mycobacterium avium subspecies paratuberculosis." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31378.
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Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a chronic enteritis that has a damaging economic and welfare impact on the livestock industry. Johne's disease in cattle is known to reduce milk yield and carcass value, making it of economic concern to both dairy and beef farmers. In addition, there is cause for concern regarding zoonotic transmission, as there is an unconfirmed but potential relationship between MAP infection and human Crohn's disease, which presents similar clinical symptoms. MAP is most often contracted by neonates through the faecal-oral route, but can also be spread through contact with contaminated milk and colostrum, as well as in utero. Once the host receives an oral dose, the bacteria traverse the gut epithelium and are phagocytosed by gut macrophages residing in the lamina propria and Peyer's patches. MAP are able to evade the macrophage response by resisting intracellular degradation within phagosomes. Infected macrophages respond to the infection by secreting several pro-inflammatory cytokines that drive the downstream immune response and granuloma formation. This work aimed to elucidate key early responses of bovine monocyte derived macrophages (MDM) to MAP infection, and determine the reliability of using the reference strain, K10 (which is likely to have undergone lab adaptation) to model the infection in vitro, by comparing the MDM response to K10 with the response to a recent clinical isolate, C49. At a multiplicity of infection of 5 (MOI 5), there was a significant decrease in K10 intracellular survival (~90%), compared to C49 intracellular survival, over a 24 hour infection time-course. This suggests that K10 may have lost some virulence mechanism through lab adaptation. Understanding the mechanisms of how MDM respond to these two strains could be informative for the design of targeted vaccines When further investigating the MDM response to both strains, it was found that, at MOI 5, MDM infected with K10 secreted higher levels of IL-1β and IL-10, compared to MDM infected with C49. Both cytokines are associated with mycobacterial infection and could perhaps indicate that MDM are more responsive to the K10 strain at early time-points. In addition, MDM infected with K10 produced significantly higher levels of reactive nitrogen species (RNS). RNS are antimicrobial products that can destroy invading pathogens, and have been shown to have bactericidal effects on MAP. The production of RNS could, therefore be a potential mechanism by which MDM are able to kill K10 more efficiently than C49. An additional aim of this project was to understand the importance of the route of phagocytosis in determining the outcome of MAP infection. MDM express several phagocytic receptors, including Fc receptors (FcRs), complement receptors (CR), Ctype lectin receptors and scavenger receptors. This project mainly focused on the role of the mannose receptor (MR) on bacterial uptake and downstream immune responses, as past studies have suggested that other species of mycobacteria such as M. tuberculosis, target the mannose receptor in order to regulate macrophage immune responses. Blocking the MR reduced intracellular survival for both strains of MAP; however, the mechanism by which the MR influences intracellular survival remains poorly understood The effect of opsonisation on MAP prior to uptake by phagocytic cells was also investigated, as presence of opsonins, such a complement proteins and antibody, can change the mechanism by which pathogens are phagocytosed. MAP were incubated in serum from either MAP- negative or MAP- positive cattle, prior to infection and the percentage uptake and survival assessed by performing colony counts. Opsonisation in serum from Johne's negative cattle resulted in marked increase in MAP uptake but not intracellular survival, whereas opsonisation in serum from Johne's positive cattle did not increase uptake but decreased the intracellular survival rate by 24 HPI. This finding highlights a potential protective role of antibody early in the infection process, and could significantly impact how the infection is modelled in future, as anti-MAP antibody may be present in contaminated milk at the point of infection. Taken together, the data presented in this thesis show that bacterial strain has a significant impact on MDM response to MAP infection, which may have important implications for the interpretation of previous studies and the design of future studies investigating host-pathogen interactions in the context of paratuberculosis. Additionally, this work has shown that RNS production and the mechanism of uptake can affect intracellular survival rates, and although this needs further investigation, the findings could have implications for the design of future vaccines.
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Marcé, Clara. "Modelling the transmission of and effectiveness of control measures for Mycobacterium avium subsp. Paratuberculosis in dairy herds." Rennes 1, 2010. http://www.theses.fr/2010REN1S047.
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Paratuberculosis is a worldwide incurable disease of ruminants resulting in a decrease in milk production and slaughter value. The aim of this thesis was to evaluate the epidemiological and economic effectiveness of selected control programmes in infected dairy herds. A stochastic simulation model has been developed to represent both the population dynamics within a dairy herd and the transmission of Mycobacterium avium subsp. Paratuberculosis (Map). It has been coupled to an existing bioeconomic model. The spontaneous within-herd progression of Map infection after the introduction of one infected cattle in an initially susceptible herd was studied in the absence of control measure. The effect of within-herd contacts on Map spread in a persistently infected herd was investigated. The cost-effectiveness of test-and-cull strategies to control Map infection in dairy herds was assessed. Simulation outcomes put forward that, even when no control measure is implemented, fadeout can occur if less than two clinically affected animals are present. In persistently infected herds, the two main transmission routes are transmission via the environment of the farm and in utero transmission. Isolating calves from their herd mates during the first weeks of age has no significant impact on Map transmission. Limiting or delaying calf exposure to adult faeces and early culling of clinically affected adults are thus recommended to decrease Map prevalence in infected dairy herds. Systematic test-and-cull appears cost-effective if implemented from the day one infected cattle is introduced. The tool designed here is flexible and enables studying other control options within a dairy herd<br>La paratuberculose est une maladie incurable des ruminants entraînant une diminution de la production laitière et de la valeur de carcasse des animaux infectés. L'objectif de ma thèse est d'évaluer l'efficacité épidémiologique et économique d'actions de maîtrise en troupeaux bovins laitiers infectés. Un modèle de simulation stochastique représentant la dynamique de population d'un troupeau bovin laitier et la transmission indirecte de Mycobacterium avium subsp. Paratuberculosis (Map) a été, élaboré puis couplé à un simulateur bioéconomique existant. L'évolution spontanée de l'infection après I'introduction d'un animal infecté dans un troupeau initialement sensible est étudiée en l'absence d'action de maîtrise. L'effet de la structure de contact sur la transmission de Map est exploré. La rentabilité de stratégies de maîtrise de l'infection est évaluée. Une extinction de l'infection peut survenir lorsque moins de deux animaux cliniquement infectés sont présents en cinq ans, en l'absence d'action de maîtrise. Dans les troupeaux infectés persistants, la transmission in utero et via l'environnement contaminé sont les deux principales voies de transmission. Empêcher le contact précoce entre veaux n'a pas d'impact sur la transmission de Map. Il est recommandé de limiter ou retarder l'exposition des veaux aux fèces des adultes et de réformer rapidement les animaux cliniquement infectés pour réduire la prévalence de l'infection. L'utilisation de tests suivis de réformes mis en place systématiquement dès l'introduction d'un animal infecté semble rentable. L'outil développé ici est flexible et permettra d'étudier d'autres actions de maîtrise en troupeau laitier
4
Millar, Douglas Spencer. "Mycobacterium paratuberculosis, mycobacteria and chronic enteritis in humans and animals." Thesis, St George's, University of London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308932.
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Bulander, Korinna. "Vergleichende Untersuchungen zum Nachweis von Mycobacterium avium ssp. paratuberculosis in Milchrinderbeständen." Giessen VVB Laufersweiler, 2009. http://d-nb.info/995997667/04.
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Okafor, Chika Chukwunonso. "Detection of Mycobacterium avium subsp. paratuberculosis IgG by a conductometric biosensor an aid in diagnosis of Johne's disease /." Diss., Connect to online resource - MSU authorized users, 2008.
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7
Elze, Julia. "Nachweis von Mycobacterium avium ssp. paratuberculosis bei Schlachtrindern." Hannover Bibliothek der Tierärztlichen Hochschule Hannover, 2010. http://d-nb.info/1000021831/34.
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Schulze, Martina. "Untersuchungen zur Stammdifferenzierung von Mycobacterium avium subsp. paratuberculosis /." Berlin : Mbv, Mensch-und-Buch-Verl, 2009. http://d-nb.info/995894671/04.
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Herthnek, David. "Molecular diagnostic methods for Mycobacterium avium subsp. paratuberculosis : more than a gut feeling /." Uppsala : Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 2009. http://epsilon.slu.se/200920.pdf.
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Pillars, Roxanne Bee. "Control strategies for Johne's disease in dairy cattle." Diss., Connect to online resource - MSU authorized users, 2008.
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Thesis (PH.D.)--Michigan State University. Large Animal Clinical Sciences, 2008.<br>Title from PDF t.p. (viewed on Aug. 28, 2009) Includes bibliographical references (p. 260-281). Also issued in print.
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Turenne, Christine. "The evolution of the pathogen «Mycobacterium avium» subsp «paratuberculosis»." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32284.
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The genus Mycobacterium is best recognized for its pathogens M. tuberculosis and M. leprae, the etiologic agents of Tuberculosis and Leprosy. Sequencing of their genomes has revealed an evolutionary process of reductive genomics. Another common species, the M. avium complex (MAC), consists of both environmental isolates that can cause opportunistic infection in humans as well as pathogenic isolates that cause disease primarily in birds and livestock. The basis of this variation in disease phenotypes is unknown. Two genome sequences representing a pathogen of cattle, M. avium subsp. paratuberculosis (MAP) and an opportunistic isolate from a human (M. avium subsp. hominissuis) have served as the foundation for the comparative genomics of MAC. This is complicated by a level of genetic variability one log greater than found within the M. tuberculosis complex (MTBC), and by the existence of other MAC subsets beyond the two sequenced strains. In this thesis, I set out to define the phylogenetic relationships of the various members of MAC and explore the evolutionary processes that led to the emergence of the pathogenic species MAP. An identification scheme was developed to unambiguously brand subsets of MAC, a tool lacking in the past thus hampering data interpretation. Expansion to a multilocus sequence analysis (MLSA) system revealed that the MAC consists of a highly variable group with most of the genotypes belonging to what is considered to be the environmental subset. However, both the avian and MAP pathogens manifested as two separate clones that have independently evolved from their larger subset. The distribution and directionality (insertion or deletion) of large se<br>Le genre Mycobacterium est mieux reconnu pour ses espèces pathogènes M. tuberculosis et M. leprae, les agents étiologiques de la tuberculose et de la lèpre. Le séquençage de leur génome a indiqué un processus évolutionnaire de réduction génomique. Des autres espèces communes, le complexe M. avium (MAC) est composé de souches environnementales qui peuvent causer des infections opportunistes chez l'homme aussi bien que de souches pathogènes qui causent la maladie principalement chez les oiseaux et le bétail. La base de cette variation phénotypique est inconnue. Deux séquences génomiques représentant le pathogène de bétail M. avium subsp. paratuberculosis (MAP) et un isolat opportuniste d'humain (M. avium subsp. hominissuis) ont servi de base pour la génomique comparative du MAC. Ceci est compliqué par un niveau de variabilité génétique d'un ordre logarithmique plus grand que celui qui se trouve dans le complexe de M. tuberculosis (MTBC), et par l'existence d'autres sous-ensembles de MAC au-delà des deux souches séquençées. Dans cette thèse, je cherche à définir les rapports phylogénétiques des divers membres du MAC et à explorer les processus évolutionnaires qui ont mené à l'apparition de l'espèce pathogène MAP. Une technique d'identification a été développée pour déterminer clairement les sous-ensembles de MAC, un outil dont l'absence par le passé limitait l'analyse des données. La possibilité d'utiliser un système d'analyse par séquençage multi-locus (MLSA) a révélé que le MAC est composé d'un groupe hautement variable avec la plus grande partie des génotypes appartenant à ce que l'on considère comme étant le$
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Rumsey, John. "SURVIVAL OF MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS IN THE POL." Master's thesis, University of Central Florida, 2004. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/3554.
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Mycobacterium avium subspecies paratuberculosis (map) is an intracellular pathogen that is known to parasitize macrophages and monocytes. Map infiltrates gastrointestinal tract host tissue where it is the known etiological agent of johne's disease in ruminants and implicated in the etiology of crohn's disease in humans. Map's ability to survive within macrophages enables it to disseminate throughout the rest of the host, possibly infecting other circulating blood leukocytes. In this study, the survival and fate of map strain atcc 43015 (human isolate) following phagocytosis was determined using in vitro murine macrophage cell line j774a.1 and polymorphonuclear cells (pmnc's) from five crohn's disease patients. Pmnc's from three healthy individuals and two ulcerative colitis patients, as well as escherichia coli (atcc 11303) and mycobacterium tuberculosis strain h37ra (atcc 25177), were included as controls (moi 10:1). Maturation of the phagosome was determined by evaluating the presence of stage specific markers on the surface of the phagosomal membrane. The endosomal protein, transferrin receptor, and the lysosomal marker, lamp-1, were then immunostained with cy-5 conjugated secondary antibodies, and colocalization of bacteria with each marker was evaluated separately using confocal scanning laser microscopy (cslm). In both tissue models, colocalization of viable map and m. Tuberculosis with the early endosomal marker, transferrin receptor occurred with an estimated five fold higher frequency than did association with the late lysosomal marker, lamp-1, as compared to live e. Coli, and all dead bacterial species. Using differential live/dead staining and fluorescent microscopy, survival of m. Tuberculosis and map was estimated at 85% and 79%, respectively compared to only 14% for e. Coli. The outcome was similar for both tissue culture and pmncs from all patients tested, suggesting that map and m. Tuberculosis can survive readily in both cell types, and regardless of the disease state of the host or the killing power of the cell. Map's survival appears to mimic m. Tuberculosis', suggesting the ability to resist phagolysosome fusion, by maintaining association with the early endosomes. Overall, the data confirms map virulence in host human blood leukocytes.<br>M.S.<br>Department of Molecular Biology and Microbiology<br>Burnett College of Biomedical Sciences<br>Molecular Biology and Microbiology
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Safavi-Khasraghi, Mitra. "EXPRESSION AND CHARACTERIZATION OF MYCOBACTERIUM PARATUBERCULOSIS 19KDA WITH POSTTRANSLATIONAL MODIFICATION." Master's thesis, University of Central Florida, 2006. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/3080.
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Despite the fact that E. coli supports limited posttranslational modification, this bacterium has been universally used as the expression system of choice. Expression of modified proteins in E. coli may lead to expression of recombinant proteins that lack essential immunomodulatory or catalytic components essentials for infectious processes. Previously in our laboratory, pMptb#28 plasmid containing a 4.8 kb insert from M. paratuberculosis has been identified which expressed 16 kDa recombinant protein in E. coli and 19 kDa recombinant protein in Mycobacterium smegmatis. The objective of this study is to identify the ORF sequence, investigate possible posttranslational modification and characterize the protein forms in the two hosts. Earlier in the study, the genome sequence for M. paratuberculosis was not available and therefore sequencing both the 5' and 3' ends of the 4.8 kb insert did not help in the identification of the ORF. However, unidirectional Exonuclease deletion resulted in identification of subclones containing possible ORF sequence. Later on, the publication of the M. paratuberculosis genome sequence along with BLAST analysis of sequences from the subclones resulted in the identification of 486 bp ORF with significant identity to that from M. tuberculosis and M. leprae. Cloning of the 486 ORF coding sequence in E. coli resulted in the expression of 16 kDa protein similar to the calculated predicted size of translated peptide. Cloning of the 486 bp ORF coding sequence in M. smegmatis resulted in the expression of 19 kDa protein similar to that from M. paratuberculosis. The 16/19 kDa forms of the same protein were verified using rabbit anti-M. paratuberculosis antibodies adsorbed in E. coli and M. smegmatis lysates. The size of the 19 kDa proteins was not reduced following treatment with deglycosylation enzymes in absence of any enzyme inhibitors. The 19 kDa product was confirmed not be a glycoprotein when failed to react with ConA stain. The 16/19 kDa forms of the protein were evaluated against T-lymphocytes from Crohn's disease patients and normal controls. T- proliferation assay included controls such as PHA and PPD from M. paratuberculosis. There was not a significant difference between the two forms of the protein (16/19 kDa) against T-cell response from both populations. Overall, the study identified the ORF of the 19 kDa non-glycoprotein from M. paratuberculosis. Moreover, this is the first study which reports that the zoonotic M. paratuberculosis supports posttranslational modification similar to M. tuberculosis and M. leprae pathogens. Although the posttranslational modification component in this 19 kDa nonglycoprotein did not affect T- cell response, the finding is significant toward glycoproteins from M. paratuberculosis and their role in the pathogenesis of this bacterial infection in animals and humans.<br>M.S.<br>Department of Molecular Biology and Microbiology<br>Burnett College of Biomedical Sciences<br>Molecular Biology and Microbiology
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Gutiérrez, Duprat Ximena Alejandra. "Detección de Mycobacterium avium subsp. paratuberculosis en caprinos de la Región Metropolitana." Tesis, Universidad de Chile, 2005. http://repositorio.uchile.cl/handle/2250/130864.
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Memoria para optar al Título
Profesional de Médico Veterinario<br>La Paratuberculosis es una enfermedad infecto contagiosa crónica con un largo período de incubación causada por Mycobacterium avium subsp. paratuberculosis (MAP), que afecta principalmente a los rumiantes, generando diarrea en algunas especies, caquexia y debilitamiento progresivo y como consecuencia, perdidas económicas en los rebaños. También infecta a animales silvestres que actuarían como posibles reservorios y se le asocia un posible potencial zoonótico, habiendo sido aislada la bacteria en algunos pacientes con la Enfermedad de Crohn, siendo el posible vehículo de infección la leche, ya que esta bacteria resistiría la pasteurización.
En este estudio se trata de detectar la presencia de Mycobacterium paratuberculosis desde heces de caprinos de la región Metropolitana.
Se realizaron cultivos bacteriológicos para M. paratuberculosis según recomendaciones del Australian Standard Diagnostic Techniques (ASDT) y con las modificaciones que permiten una mejor eficiencia en la recuperación de la bacteria. El medio de cultivo para aislamiento primario es el medio de Herrold con yema de huevo (HEYM) más mycobactina J.
Se tuvo acceso a 10 rebaños donde se seleccionaron el número de animales en múltiplos de cinco, tratando de abarcar el 25% de la población de cada rebaño. Se recolectaron muestras directamente desde el recto, tomando 1 a 2 heces de cada caprino, que se depositaron en bolsas de plástico estéril agrupándose en “pools” de cinco animales. Para tener una mayor probabilidad de detectar rebaños caprinos infectados con MAP, se consideraron hembras mayores de un año, y en lo posible animales que hayan presentado signos de diarrea, debilitamiento, pérdida de peso progresiva, disminución de la producción láctea, etc. Se comprobó la presencia de MAP desde heces de caprinos de la Región Metropolitana en 3 rebaños de los 10 muestreados, encontrándose un 18% de los “pools” positivos a MAP. El medio HEYM más la adición de mycobactina J demostró claramente ser muy efectiva para el aislamiento del MAP a partir de muestras de heces de animales que ya estaban diseminando el microorganismo
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CHARLES, JEAN-DOMINIQUE. "Mycobacterium paratuberculosis et maladie de crohn : a propos d'une observation." Lyon 1, 1990. http://www.theses.fr/1990LYO1M245.
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Begg, Douglas, and n/a. "Immune profiles in sheep following experimental infection with Mycobacterium paratuberculosis." University of Otago. Department of Microbiology & Immunology, 2005. http://adt.otago.ac.nz./public/adt-NZDU20070427.142318.
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Johne�s disease in ruminants is caused by the pathogenic bacterium Mycobacterium avium subspecies paratuberculosis. An experimental infection model in sheep was developed as a prelude to the testing of new vaccines and the development of improved diagnostic assays for Johne�s disease. The final challenge model developed used four doses of 10⁹ viable organisms given at two to three day intervals. Gross and microscopic lesions were found in a high proportion of sheep (80%) at ten months post challenge. There was considerable variation in immune responses from animals challenged with different strains of M. paratuberculosis. Sheep challenged with a low passage laboratory culture of strain (W) M. paratuberculosis, produced strong lymphocyte transformation responses and Interferon gamma (IFN-γ) production at two months post challenge. Subsequent necropsy and culture from intestinal tissues showed only a low level of infection (25%). In comparison a primary tissue isolate of M. paratuberculosis (JD3) resulted in higher (60-90%) infection rates in orally challenged animals. The immune profile from these animals showed very little reactivity for the first three months post challenge, after which IFN-γ production could be detected. Antibody production and lymphocyte transformation response could not be measured until at least seven months post challenge. Sheep challenged with the primary tissue isolate instilled directly into the tonsil resulted in equivalent levels of Johne�s disease to those obtained with oral challenge. However, intratonsillar challenge resulted in higher levels of immune reactivity than oral challenge.
The proprietary Johne�s vaccines; NeoparsecTM and GudairTM and an Aqueous vaccine were tested in sheep. The immunological reactions of the sheep to these vaccines showed some variations between the two separate studies, with the NeoparasecTM and GudairTM vaccines evoking high levels of CMI and humoral reactivity within two months of vaccination. Detailed immunological examination of gut associated lymphoid tissues were carried out on subgroups of animals that were either vaccinated or non-vaccinated and went on to develop disease or were immune to experimental challenge. The results showed that the diseased animals examined had multibacillary lesions and strong CMI and humoral responses. There were decreased proportions of CD4⁺, CD8⁺ and CD25⁺ T cells in peripheral blood and gut associated lymphatics of diseased animals compared with the immune or unchallenged subgroups. Profiles from the immune subgroups showed a stronger lymphocyte transformation response than case matched diseased animals. Tissues from immune animals showed increased proportions of B cells above those seen in diseased or unchallenged animals. This study has resulted in the development of a robust experimental sheep model in which Johne�s disease occurs in a high proportion of challenged animals. Critical time points for the establishment of infection or disease have been determined. It can be used in the future to evaluate protective efficacy of vaccines or to critically chart immunological profiles that are associated with infection, disease or protective immunity. Considerable research is needed to develop improved diagnostic tests to identify patterns of immunity during the early stages of infection or while the animal has subclinical disease.
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Lei, Liying. "Role of dendritic cells in Mycobacterium avium subspecies paratuberculosis infection." [Ames, Iowa : Iowa State University], 2007.
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Elze, Julia [Verfasser]. "Nachweis von Mycobacterium avium ssp. paratuberculosis bei Schlachtrindern / Julia Elze." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2010. http://d-nb.info/1000021831/34.
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Schulze, Martina [Verfasser]. "Untersuchungen zur Stammdifferenzierung von Mycobacterium avium subsp. paratuberculosis / Martina Schulze." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/102370840X/34.
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Lalande, Jean-Daniel. "NOD2 mediates innate and adaptive immunity to «Mycobacterium avium paratuberculosis»." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106471.
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Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a chronic granulomatous enteritis of ruminants. MAP has been specifically and significantly associated with Crohn's disease (CD), a human enteritis with similarities to paratuberculosis. While these observations do not attest to causality of disease, they have potentiated efforts to investigate whether CD-susceptibility genes play a role in MAP infection. Specifically, our interests lie in the gene NOD2. NOD2 is part of the NOD-like receptor family and is involved in innate recognition of muramyl dipeptide (MDP), a component of bacterial peptidoglycan. Interestingly, CD-associated polymorphisms abrogate this response. In addition, NOD2 appears to be especially sensitive to mycobacterial MDP; thus we hypothesized that NOD2 would play a role in control of MAP infection. Using Nod2-/- mice as models of human NOD2 deficiency, we tested ex vivo and in vivo bacteriological, immunological and pathological phenotypes in response to MAP infection. Stimulation of peritoneal Nod2-/- macrophages revealed impaired innate recognition of MAP, a phenotype not seen when using Escherichia coli. Furthermore, we consistently observed higher burdens of MAP (~0.3 log) in Nod2-/- macrophages cell culture at 5 days post-infection; E. coli intracellular growth was NOD2-independent. Four weeks following intraperitoneal MAP infection, NOD2 disruption led to weakened adaptive immune responses towards infection as evidenced by diminished MAP-specific IFN-γ producing cells. Moreover, Nod2-/- splenocytes provided no anti-mycobacterial benefit in MAP-infected macrophage co-culture, as opposed to Nod2+/+ splenocytes which were directly responsible for a ~0.5 log reduction in MAP burden. During long-term investigations, we observed mesenteric adenitis, but no gut pathology following a 1 year MAP-infection in Nod2+/+ and Nod2-/- and a 6 month infection in Cybb-/- mice, despite isolation of organisms from mesenteric lymph nodes. In contrast, Irf-1-/- mice showed impaired elimination of MAP. Taken together, NOD2 is involved in control of intracellular growth of MAP and disruption leads to impaired innate and adaptive immune responses towards MAP infection. The subtle nature of this pathogen indicates that Nod2-/- and Cybb-/- are unlikely to serve as tractable murine models of paratuberculosis. However, Irf-1 disruption did lead to enhanced persistence of MAP.<br>Mycobactérium avium paratuberculosis (MAP) est l'agent causal de la paratuberculose, une entérite granulomateuse chronique chez les ruminants. MAP a été spécifiquement et significativement associé à la maladie de Crohn, une entérite chez les humains qui est semblable à la paratuberculose. Alors que ces observations ne prouvent pas une causalité entre la bactérie MAP et la maladie de Crohn, elles ont potentialisé des investigations dans le but de déterminer si les gènes reliés à la maladie de Crohn jouent un rôle lors d'une infection à MAP. Spécifiquement, nous sommes intéressés au gène NOD2. NOD2 fait partie de la famille des récepteurs NOD-like et est impliqué dans la reconnaissance innée de muramyl dipeptide (MDP), un composant de la peptidoglycane bactérienne. Il est intéressant de noter que les mutations au gène NOD2 qui sont associées à la maladie de Crohn abolissent cette réponse. De plus, il a été démontré que NOD2 est extrêmement sensible au MDP mycobactérien; ainsi nous avons fait l'hypothèse que NOD2 joue un rôle dans le contrôle d'une infection à MAP. En utilisant une souche de souris Nod2-/- comme modèle pour la déficience de NOD2 chez les humains, nous avons évalué les phénotypes bactériens, immunologiques et pathologiques ex vivo et in vivo, par rapport aux infections à MAP. La stimulation de macrophages péritonéales provenant de souris Nod2-/- a révélé une déficience dans la reconnaissance innée de MAP, un phénotype qui n'était pas présent lors de stimulation avec Escherichia coli. En plus, nous avons constamment observé un taux de MAP plus élevé (~0.3 log) dans les cultures de macrophages Nod2-/- 5 jours après l'infection; la croissance intracellulaire de E. coli était indépendant de NOD2. Quatre semaines suivant une infection intrapéritonéale de MAP, la perturbation de NOD2 a affaibli les réponses immunitaires adaptatives envers l'infection de MAP. Ceci était caractérisé par une réduction de cellules spécifique à MAP produisant de l'IFN-γ. Aussi, les splénocytes de génotype Nod2-/- n'ont fourni aucun avantage anti-mycobactérienne lors de co-culture avec des macrophages infectés avec MAP. Au contraire, les splénocytes Nod2+/+ étaient directement responsable d'une réduction de ~0.5 log de MAP. Ces observations nous ont mené à poursuivre des investigations de pathologie d'infection de MAP à long-terme. Malheureusement, nous n'avons pas observé de pathologie touchant les intestins de souris infectés chroniquement à MAP pendant 1 ans, malgré l'isolation d'organismes dans les ganglions mésentériques. De façons similaires, les souris Cybb-/- ont développé une adénite mésentérique chronique, avec pathologie intestinale mineure, lors d'une infection de 6 mois de MAP. Par contre, l'infection de souris Irf-1-/- a révélé une déficience dans le contrôle d'infection à MAP. Pris dans leur ensemble, NOD2 est impliqué dans le contrôle de la croissance intracellulaire de MAP et sa perturbation mène à la déficience de réponses innées et adaptatives envers MAP. La nature subtile de ce pathogène nous a révélé que les souris Nod2-/-et Cybb-/- ont peu de chance de servir de modèle utile de la paratuberculose chez les souris, mais la perturbation de Irf-1 à causé une augmentation dans la persistance de MAP.
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Kreitmann, Louis. "Investigations of Irgm1 during experimental infections with «Mycobacterium avium paratuberculosis»." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121520.
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Introduction: Mycobacterium avium paratuberculosis (MAP) is the causative agent of a chronic granulomatous enteritis of ruminants called Johne's disease (JD). Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology affecting humans. Due to histological similarities between the two conditions, it has been suggested that MAP could be responsible for a subset of cases of CD. Irgm1 (murine ortholog of IRGM, a CD susceptibility gene) has been linked to host defence against mycobacteria. Methods: In the first part of this work, we have attempted to study the immune response of the Irgm1-/- mouse to systemic infection with MAP. In the second part, we have attempted to use the Irgm1-/- mouse as a host susceptible to lead to significant pathology after intra-intestinal infection with MAP (a murine model of JD) and documented its response to therapeutics used in the care of patients with CD. Results: First, we have shown that mice deleted for Irgm1 have a major susceptibility to systemic MAP infection, with accelerated rate of death and uncontrolled bacterial replication. To explain this, we have identified a defect of Irgm1-/- macrophages in controlling the intracellular growth of MAP. We have also identified severe haematological abnormalities leading to their death. Second, we have devised a protocol for the surgical inoculation of ~ 109 MAP colony forming units (CFUs) in the jejunum of Irgm1-/- mice. After 1 and 2 months of infection, we have observed significant intestinal histopathological lesions resembling those seen in Johne's disease, including focal and transmural lympho-histiocytic infiltrates and mesenteric lymphadenopathy. Mice infected according to this protocol were submitted to: 1) a systemic treatment with methylprednisolone, which did not lead to increased mortality; and 2) a treatment with an anti-tumor necrosis factor-alpha (TNF-α) antibody, which did not lead to uncontrolled MAP replication in the host.Conclusion: Irgm1-/- mice are markedly susceptible to systemic MAP infection. When inoculated with ~ 109 MAP CFUs in the lumen of the jejunum, they develop stable histological lesions resembling those of JD. Interestingly, treatments used in the cure of patients with CD did not have a deleterious effect.<br>Titre du mémoire : Etude du rôle d'Irgm1 au cours d'infections expérimentales par Mycobacterium avium paratuberculosis Introduction : Mycobacterium avium paratuberculosis (MAP) est responsable d'une entérite chronique granulomateuse chez les ruminants, la maladie de Johne (ou paratuberculose). La maladie de Crohn est une maladie inflammatoire chronique du tube digestif d'étiologie indéterminée qui affecte les humains. Du fait de similarités histologiques entre les deux conditions, il a été suggéré que MAP pouvait être responsable de certains cas de maladie de Crohn. Irgm1 (orthologue murin de IRGM, un gène de susceptibilité à la maladie de Crohn), a été impliqué dans la réponse immunitaire contre les mycobactéries. Méthodes : Dans la première partie de ce travail, nous avons étudié la réponse immunitaire de la souris Irgm1-/- au cours d'une infection systémique par MAP. Dans la second partie, nous avons cherché à utiliser la souris Irgm1-/- pour induire des lésions histologiques après infection intra-intestinale par MAP (réalisant un modèle murin de maladie de Johne), et avons documenté la réponse de ce modèle à des traitements utilisés chez les patients atteints de maladie de Crohn. Résultats : Nous avons montré que la souris Irgm1-/- présente une susceptibilité majeure à une infection systémique par MAP, avec mortalité accélérée et réplication bactérienne incontrôlée. Nous avons identifié un défaut des macrophages Irgm1-/- à contrôler la croissance intra-cellulaire de MAP. Nous avons aussi identifié des anomalies hématologiques expliquant leur mortalité accélérée. Dans un second temps, nous avons conçu un protocole consistant en l'injection par voie chirurgicale de ~ 109 unités formant colonies (UFC) de MAP au sein de la lumière du jéjunum de souris Irgm1-/-. Nous avons observé qu'à 1 et 2 mois post-infection, nous avions induit des lésions histologiques ressemblant à celles rencontrées dans la maladie de Johne, notamment des infiltrats lympho-histiocytiques focaux et transmuraux et une lymphadénopathie mésenterique. Des souries infectées selon ce protocole ont été soumises à: 1) un traitement systémique par methylprednilosone, qui n'a pas entrainé une augmentation de la mortalité; et 2) un traitement par anticorps anti-tumor necrosis factor-alpha (TNF-α), qui n'a pas provoqué une réplication bactérienne incontrôlée. Conclusion : Les souris Irgm1-/- sont susceptibles à une infection systémique par MAP. Après inoculation par voie chirurgicale de ~ 109 UFC de MAP, elles développent des lésions histologiques stables analogues à celles de la maladie de Johne. Des traitements utilisés pour traiter la maladie de Crohn n'ont pas entrainé d'effet délétère. Des travaux supplémentaires sont nécessaires pour évaluer l'utilité de ce modèle dans les recherches sur la maladie de Johne et sur la maladie de Crohn.
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Martinho, António Pedro Alegre. "Rastreio de mycobacterium avium subsp. paratuberculosis na doença de Crohn." Master's thesis, [s.n.], 2012. http://hdl.handle.net/10284/3571.
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Trabalho apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas<br>O possível envolvimento de Mycobacterium avium subsp. paratuberculosis (MAP) na etiologia da doença de Crohn tem gerado muita controvérsia ao longo dos anos. A utilização de métodos de identificação por PCR reportou a detecção de MAP em pacientes com doença de Crohn, mas também em indivíduos sem doença. Outros estudos reportam resultados negativos para ambos os grupos. O objectivo deste trabalho foi verificar se na população de doentes estudada se encontrava uma associação entre presença de MAP e DC.
Efectuou-se detecção de MAP em 29 amostras de sangue periférico: 11 amostras de pacientes com doença de Crohn e 18 amostras de indivíduos controlos. As amostras foram analisadas por desagregação das células e extracção do DNA tendo sido, de seguida, utilizada a técnica de PCR-nested para amplificação de parte da sequência de inserção IS900, específica do MAP e presente em elevado número de cópias. A análise dos produtos amplificados foi efectuada por electroforese em gel de agarose. DNA de MAP foi detectado em 9 dos 11 pacientes (82%) e 4 dos 18 controlos (22%), o que sugere uma associação entre MAP e DC na população estudada.
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Ghadiali, Alifiya H. "Studies on Mycobacterium avium subsp. paratuberculosis genotypic and phenotypic variations /." Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1110229469.
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Thesis (Ph. D.)--Ohio State University, 2005.<br>Document formatted into pages; contains xxi, 216 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 March 9.
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Dalto, André Gustavo Cabrera. "Achados clínicos e patológicos de paratuberculose em búfalos (Bubalus bubalis) no Rio Grande do Sul - Brasil." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/32134.
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Descrevem-se os aspectos epidemiológicos e clínico-patológicos da paratuberculose em um rebanho de búfalos no Município de Guaíba no Rio Grande do Sul. A propriedade possuía cento e noventa e quatro búfalos principalmente da raça mediterrâneo e destinava-se a produção de leite e carne. No período de abril de 2009 a setembro de 2010 seis búfalos apresentaram diarreia crônica intermitente, perda de peso e apetite normal. Na neccropsia observaram-se vasos linfáticos proeminentes no mesentério e na mucosa do intestino. Os linfonodos mesentéricos estavam moderadamente aumentados, com áreas escuras entremeadas com focos multinodulares brancacentos, principalmente na região cortical. A mucosa do intestino se encontrava espessa e cerebriforme. Ao exame histológico, desde o duodeno até o intestino grosso havia infiltrado composto principalmente por macrófagos epitelióides e, em menor escala, linfócitos, plasmócitos e células gigantes tipo Langhans. Outros achados observados foram dilatação dos vasos linfáticos, linfangite granulomatosa e linfangiectasia. Nos linfonodos mesentéricos verificaram-se lesões histológicas semelhantes. A coloração de Ziehl-Neelsen e a imuno-histoquimica revelaram bacilos álcool-ácido resistentes no interior de macrófagos, de células gigantes de Langhans e livres na mucosa e submucosa do intestino e dos linfonodos mesentéricos. Mycobacterium avium subsp. paratuberculosis foi isolado em cultivo bacteriano de amostras de fezes, raspado de mucosa intestinal e de linfonodos mesentéricos. A identificação do agente foi realizada pela técnica de PCR IS900. Foi realizado, também, levantamento sorológico de 136 búfalos da propriedade através da técnica de ELISA, na qual foram observados 15,45 % reagentes. O diagnóstico da paratuberculose foi baseado nos dados clínicopatológicos, sorologia, isolamento e identificação do agente.<br>It´s described the epidemiologic, clinical and pathologic aspects of paratuberculosis in a bubaline herd in Guaiba city, southern Brazil. The property had one hundred and ninety animals for milk and meet production. Six adults Mediterranean breed bubalines showed chronic intermittent diarrhea, lost of weight and normal appetite. At necropsy, the lymphatic vessels were prominent in the serosa, the mesenteric lymphnodes were slightly enlarged with dark areas interwoven by multinodular white spots mainly in the cortical region. The intestine mucosa were thickened and of corrugated aspect. The microscopic exam revealed severe diffuse granulomatous inflammation, marked dilatation of the lymphatic vessels, granulomatous lymphangitis and lymphangioectasia from the duodenum to the large bowl. The mesenteric lymphnodes showed similar histological lesions. Acid-fast bacilli in macrophages, in Langhans giant cells and freely in the mucosa and submucosa of the small intestine and lymphnodes were shown at Ziehl-Neelsen staining and immunohistochemistry. Mycobacterium avium subsp. paratuberculosis was isolated through bacterial cultivation of samples taken from feces, intestinal mucosa, mesenteric lymphnodes, and identified through IS900 PCR. In addition, a serologic survey was performed in the property by ELISA test. 15.45 percent of the animals reacted positive to the test. The diagnosis of paratuberculosis was based on clinical, pathological and epidemiological data, serology exam, bacterial isolation and identification of the agent.
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Heaslip, Darragh G. "Studies on a 34kDa protein of M. avium subsp. paratuberculosis, a putative virulence factor." Thesis, University of Surrey, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247997.
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Souza, Paula Carolina de [UNESP]. "Atividade anti - Mycobacterium tuberculosis intra e extra celular e citotoxicidade dos complexos de coordenação de metais." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/94800.
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souza_pc_me_arafcf.pdf: 1133784 bytes, checksum: 02f70c3dafbe0953dabe3934d0e053a7 (MD5)<br>A tuberculose (TB) é uma doença infecciosa que tem como principal patógeno o Mycobacterium tuberculosis e continua sendo um importante problema de saúde pública mundial, exigindo o desenvolvimento de estratégias para o seu controle. Em 2011 foram notificados 8,7 milhões de casos da doença no mundo. Ao longo dos anos o cenário da doença não tem se mostrado otimista, devido ao aumento de número de casos de TB multi resistente a fármacos (TB-MDR) e o surgimento de cepas de resistência estendida (TB-XDR). A pesquisa de novos fármacos, em um contexto geral, apresenta-se como um enorme desafio científico para a era moderna. Neste sentido, a Química Inorgânica Medicinal tem se mostrado uma ferramenta bastante promissora. Este trabalho objetivou a caracterização da atividade anti- M. tuberculosis intra e extracelular e a citotoxicidade de 158 compostos de coordenação com metais. A citotoxicidade usando linhagens celulares de macrófago (J774A.1) e células epiteliais (VERO) também foi investigada. Diante Os resultados demonstraram que 16 compostos apresentaram uma alta seletividade, ou seja, alta atividade contra o bacilo da tuberculose e baixa citotoxicidade frente às linhagens testadas. Quatro desses 16 compostos selecionados foram analisados quanto a atividade intracelular; dos quais 2 compostos de coordenação de Co (cobalto) mostraram-se promissores quanto a esta atividade. Com base nos resultados encontrados mais estudos serão realizados a fim de garantir a eficácia e segurança desses novos compostos de coordenação candidatos à fármacos para tratamento da tuberculose<br>Not available
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Souza, Paula Carolina de. "Atividade anti - Mycobacterium tuberculosis intra e extra celular e citotoxicidade dos complexos de coordenação de metais /." Araraquara, 2013. http://hdl.handle.net/11449/94800.
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Orientador: Fernando Rogério Pavan<br>Banca: Patricia Bento da Silva<br>Banca: Jean Leandro dos Santos<br>Resumo: A tuberculose (TB) é uma doença infecciosa que tem como principal patógeno o Mycobacterium tuberculosis e continua sendo um importante problema de saúde pública mundial, exigindo o desenvolvimento de estratégias para o seu controle. Em 2011 foram notificados 8,7 milhões de casos da doença no mundo. Ao longo dos anos o cenário da doença não tem se mostrado otimista, devido ao aumento de número de casos de TB multi resistente a fármacos (TB-MDR) e o surgimento de cepas de resistência estendida (TB-XDR). A pesquisa de novos fármacos, em um contexto geral, apresenta-se como um enorme desafio científico para a era moderna. Neste sentido, a Química Inorgânica Medicinal tem se mostrado uma ferramenta bastante promissora. Este trabalho objetivou a caracterização da atividade anti- M. tuberculosis intra e extracelular e a citotoxicidade de 158 compostos de coordenação com metais. A citotoxicidade usando linhagens celulares de macrófago (J774A.1) e células epiteliais (VERO) também foi investigada. Diante Os resultados demonstraram que 16 compostos apresentaram uma alta seletividade, ou seja, alta atividade contra o bacilo da tuberculose e baixa citotoxicidade frente às linhagens testadas. Quatro desses 16 compostos selecionados foram analisados quanto a atividade intracelular; dos quais 2 compostos de coordenação de Co (cobalto) mostraram-se promissores quanto a esta atividade. Com base nos resultados encontrados mais estudos serão realizados a fim de garantir a eficácia e segurança desses novos compostos de coordenação candidatos à fármacos para tratamento da tuberculose<br>Abstract: Not available<br>Mestre
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Herthnek, David. "Detection and confirmation of Mycobacterium avium subsp. paratuberculosis in clinical samples /." Uppsala : Dept. of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 2006. http://epsilon.slu.se/10210535.pdf.
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Thanigachalam, Saisathya. "Dubious role of Mycobacterium paratuberculosis in pathogenesis of Type I diabetes." Master's thesis, University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5528.
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INTRODUCTION: Type 1 Diabetes Mellitus (T1DM) is a chronic disorder with unknown etiology and associated with insulin deficiency. Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of paratuberculosis in cattle, has been implicated in many autoimmune diseases including Crohn's disease, TIDM and others. We hypothesize that the molecular mimicry including epitope homology between MAP-Hsp65 and pancreatic Glutamic Acid Decarboxylase65 (GAD65) may play a role in the auto destruction of pancreatic beta cells leading to insufficient insulin production and the development of TIDM, following exposure to MAP. METHODOLOGY: Peptide sequences of MAP-Hsp65 and GAD65 were analyzed using BLAST and PyMOL bioinformatics tools. Cross reactivity between the two proteins were evaluated using immunoblot and ELISA. Furthermore, coded EDTA blood samples were collected from 18 subjects (12 DM and 6 controls) and investigated for the presence or exposure to MAP. Peripheral leukocytes were investigated for harboring viable MAP using long-term culture followed by nested PCR. Clinical plasma samples were used for measurement of anti-MAP IgG titer as well as glucose and Insulin concentrations. Moreover, coded bovine sera from 100 cattle (50 MAP infected and 50 healthy) were investigated for possible correlation between MAP infection and plasma levels of glucose and insulin. RESULT: Peptide BLAST analysis revealed a 44% identity between MAP Hsp65 and GAD65 proteins with 75% positive identities in a 16 amino acid region. PyMOL 3-D structural analyses identified a shared epitope region within the 16 amino acid motif which is known to be an antigenic site on GAD65 antigen. MAP DNA and anti-MAP IgG were detected in the blood of TD8, a TIDM subject. Strong cross reactivity was observed between plasma from TD8 and MAP Hsp65 in proteins samples from M. tuberculosis, and E. coli recombinant clone expressing MAP Hsp65. A weak cross reactivity was also observed between rat pancreatic tissue homogenate and rabbit anti-MAP IgG. Long term culture of leukocytes from 18 blood samples resulted in the detection of MAP in 3/10 (30%) TIDM and 4/8 (50%) control subjects whereas anti-MAP IgG were detected in 5/10 (50%) TIDM samples compared to 3/8 (37.5 %) controls. In MAP infected cattle, insulin level ranged from below 0.1ng/ml to 2.456 ng/ml with an average of 0.36 +/- 0.57ng/ml compared to 0.1ng/ml to 13.47ng/ml with an average of 2.86 +/- 3.00ng/ml in healthy cattle (P<0.0001). CONCLUSION: We identified and confirmed a shared epitope region between MAP Hsp65 and human pancreatic GAD65. The shared epitope is a known antigenic binding site. Although MAP DNA was detected in both TIDM and control subjects, a strong correlation was found between anti-MAP IgG titer and MAP-positive culture in clinical samples, regardless of diagnosis. The correlation between MAP infection and insulin level in cattle is significant. Overall the result is intriguing and requires further investigation of MAP in well-characterized clinical samples.<br>M.S.<br>Masters<br>Molecular Biology and Microbiology<br>Medicine<br>Molecular and Microbiology
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Judge, Johanna. "Rabbits (Oryctolagus cuniculus) as a host of Mycobacterium avium subspecies Paratuberculosis." Thesis, University of York, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438079.
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Lefrançois, Louise. "Etude des adhésines HBHA et LBP impliquées dans l'interaction de Mycobacterium avium ssp. paratuberculosis avec les cellules épithéliales intestinales, cibles privilégiées de la bactérie in vivo." Thesis, Tours, 2012. http://www.theses.fr/2012TOUR4020/document.
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Mycobacterium avium ssp. paratuberculosis (Map), agent étiologique de la paratuberculose, a évolué en deuxtypes dénommés, S pour« Sheep » et C pour « Cattle ». L’intestin grêle est le site primaire de l’infection à Map mais les mécanismes moléculaires impliqués dans l’implantation du bacille restent largement méconnus. L’objectif de mon projet de thèse visait à identifier et caractériser les adhésines exprimées par Map par des approches génétiques et biochimiques. J’ai ainsi purifié la HBHA et la LBP par chromatographie d’affinité puis les ai identifiés en spectrométrie de masse. L’originalité de ce travail repose sur le polymorphisme de ces adhésines observé entre les souches de type C et S. Cette variabilité a été mise en évidence sur le domaine d’interaction avec les sucres sulfatés de la cellule hôte influençant l’affinité des adhésines pour l’héparine. Ce travail de thèse a permis de caractériser pour la première fois ces deux adhésines produites par Map. Le polymorphisme de la HBHA et de la LBP, discriminant les types C et S, ouvre de nombreuses perspectives sur l’évolution de l’espèce M. avium et le rôle de ces adhésines sur le tropisme intestinal, la préférence d’hôte de Map ou encore leur potentiel diagnostic<br>Mycobacterium avium subsp. paratuberculosis (Map), the etiological agent of paratuberculosis, has evolved into two types called, S for "Sheep" and C for "Cattle." The small intestine is the primary site of Map infection but the molecular mechanisms involved in the establishment of bacilli are still unknown. The aim of my thesis was to identify and characterize the adhesins expressed by Map by genetic and biochemical approaches. I purified HBHA and LBP by affinity chromatography then identified them by mass spectrometry. The originality of this work is based on the polymorphism of these adhesins observed between strains of type C and S. This variability has been demonstrated in the binding domain involved in interaction with sulfated sugars of host cell influences adhesins affinity for heparin. This thesis has characterized for the first time these two adhesins produced by Map. Specific polymorphism highlighted related to the evolution of the species avium, opens large number questions on their role on the pathogenesis of Map including the cellular tropism, host preference or interest of these antigens to improve diagnostic
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Füllgrabe, Regina A. R. "Untersuchungen zum kulturellen und molekularbiologischen Nachweis von Mycobacterium avium ssp. paratuberculosis (MAP) aus humanen Darmbioptaten." Giessen VVB Lauferweiler, 2008. http://d-nb.info/993780016/34.
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Dudemaine, Pier-Luc. "Étude de l'état immunitaire des vaches laitière atteintes de la paratuberculose bovine." Mémoire, Université de Sherbrooke, 2013. http://hdl.handle.net/11143/6298.
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La paratuberculose bovine, ou maladie de Johne, est une maladie inflammatoire intestinale chronique provoquant d’importantes pertes économiques chez les producteurs de ruminants du monde entier. Que ce soit chez la vache laitière ou de boucherie, ces pertes sont causées majoritairement par une diminution de la capacité de reproduction, la baisse de production laitière et l’amaigrissement des vaches qui perdent ainsi beaucoup de valeur à l’abattage, en plus d’être sujettes à une réforme précoce. Outre les pertes économiques, le potentiel de transmission à l’humain est un facteur non négligeable en plus d’un risque de contamination de la chaîne alimentaire. Cette maladie est causée par une bactérie intracellulaire obligatoire nommée Mycobacterium avium subspecies paratuberculosis (MAP). II n’existe actuellement aucune stratégie efficace pour combattre l’infection chez les animaux atteints. L’évolution lente de la maladie fait en sorte que les signes cliniques apparaissent tardivement, soit plusieurs années (4 à 7 ans) après l’infection initiale. Au cours de cette progression, les animaux infectés commencent à excréter le pathogène dans leur environnement. Les animaux atteints deviennent infectieux et peuvent contaminer d’autres congénères, ainsi que leur propre veau. Afin de permettre aux producteurs d’éliminer les vaches atteintes avant qu’elles n’atteignent ce stade, il s’avère important d’établir un diagnostic précoce. Actuellement, ce n’est qu’en phase sous-clinique avancée que les tests diagnostiques sont plus sensibles, soit 2 à 3 ans après le début des excrétions fécales chez les animaux infectés. L'incompréhension du manque de sensibilité des tests de dépistage et de l'évolution de cette maladie justifient les efforts de recherche dans ce domaine en vue de mieux comprendre les réponses immunitaires impliquées dans cette maladie. En effet, une meilleure connaissance des processus d’inflammation chronique pourrait aider à développer des outils diagnostiques complémentaires. Nos résultats suggèrent une dérégulation de la réponse immunitaire. Ainsi, en étudiant les composantes et caractéristiques du sang provenant de vaches infectées, il nous a été possible d’observer que les niveaux de cytokines plasmatiques telles l’interleukine 17 et l'ostéopontine se trouvent sécrétées à différents niveaux chez les vaches atteintes de paratuberculose bovine. De plus, l'analyse de la capacité de leur sérum à soutenir efficacement la prolifération des cellules mononucléées du sang périphérique révèle que le sérum de vaches infectées interfère pour atténuer la prolifération cellulaire. II semble qu’un constituant du sérum provoque une diminution de la réponse immunitaire chez les vaches malades. Les résultats offrnt une appréciation des dérèglements immunitaires provoqués par la paratuberculose bovine.
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Moolji, Jalaluddin. "Transposon mutagenesis of «Mycobacterium avium» subsp. «paratuberculosis» to investigate potential pathogenicity islands." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95051.
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Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a highly prevalent chronic intestinal disease of cattle. It is also the putative cause of Crohn's disease, a chronic inflammatory bowel disease of humans. The MAP genome contains six segments of DNA called large sequence polymorphisms (LSPP) that are not present in its closest evolutionary relatives and were probably acquired through horizontal gene transfer. Together, they comprise 125kb, or 2.5% of the MAP genome, and contain 96 open reading frames. A detailed analysis of MAP evolution led us to hypothesize that the LSPP are pathogenicity islands, encoding genes important for MAP survival or replication in the host. To test this hypothesis, we generated a 5,000-member transposon-mutant library in MAP K-10 and developed a PCR screening method to identify potential mutants of LSPP genes. We succeeded in isolating a mutant of MAP3776c, which encodes a putative zinc siderophore. It is part of a putative five-gene zinc uptake operon that occupies almost the entirety of the insertion sequence, LSPP15. The MAP3776c mutant does not appear to have in vitro growth defects, and it is able to colonize the livers and spleens of C57Bl/6 mice within one week of intraperitoneal infection. Upcoming data from an ongoing, long-term experiment will determine whether the mutant has altered ability to persist in mice. The mutant of MAP3776c and the transposon-mutant library are useful tools for research on MAP genomics and pathogenicity that might ultimately contribute to improvements in vaccines and immunodiagnostics for Johne's disease.<br>Titre de la thèse : La Mutagénèse de Transposon de Mycobacterium avium sous-espèce paratuberculosis pour Investiguer des Zones de Pathogenicité Potentielles. Résumé : Mycobacterium avium sous-espèce paratuberculosis (MAP) est l'agent causal de la maladie de Johne, une maladie chronique intestinale des bétails très répandue. C'est aussi l'agent causal putatif de la maladie de Crohn, une maladie inflammatoire de l'intestin chronique chez l'humain. Le génome de MAP contient six segments d'ADN appelés des grands polymorphismes de séquences (LSPP) qui ne sont pas présents chez les cousins évolutionnaires de cette bactérie et qui furent probablement obtenus par transfert génique horizontal. Ensembles, ils constituent 125kb soit 2,5% du génome de MAP, et contiennent 96 cadres de lecture ouverts. Une analyse approfondie de l'évolution de MAP nous a mené à supposer que les LSPP sont des zones de pathogenicité qui codent des gènes importants pour la survie et la réplication de MAP dans l'hôte. Afin de tester cette hypothèse, nous avons produit une banque de mutants de transposon de MAP de 5 000 membres, et nous avons mis au point des conditions de réaction en chaîne par polymérase (PCR) pour identifier des mutants potentiels des gènes LSPP. Nous avons réussi à isoler un mutant de MAP3776c, qui encode un sidérophore de zinc. Ce dernier fait partie d'un opéron de cinq gènes pour un système de captation zinc qui prend presque la totalité de la séquence d'insertion LSPP15. Le mutant ne semble pas avoir de défauts de croissance in vitro, et il est capable de coloniser les foies et les rates des souris C57Bl/6 en une semaine à la suite d'une infection intrapéritonéalle. Les données d'expériences en cours à long terme détermineront si le mutant a une capacité modifiée à persister dans les souris. Le mutant de MAP3776c et la banque de mutants de transposon sont des outils avantageux pour la recherche sur la génomique e
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Plamondon, Eveline. "Thermorésistance de Mycobacterium avium ssp. paratuberculosis dans les produits de la viande." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26289/26289.pdf.
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Mycobacterium avium ssp. paratuberculosis (Map) est responsable de la maladie de Johne chez les ruminants en particulier chez le bovin. Les scientifiques ont émis l’hypothèse que Map pourrait être l'agent étiologique de la maladie de Crohn chez l'humain, ce qui a soulevé des inquiétudes en santé publique. Map est particulièrement résistant à la chaleur dans le lait, mais l'état des connaissances est pratiquement limité dans les matrices de viande. Les valeurs D (temps de réduction décimal) et z (sensibilité à la température) ont été déterminées dans du boeuf haché préparé aseptiquement à partir du muscle semi membranosus pour Map, Escherichia coli et Enterococcus faecalis. L'objectif de ce travail est de déterminer l'effet de divers traitements thermiques sur la cinétique de destruction de Map dans la viande afin d'évaluer si les procédés thermiques industriels (la pasteurisation, cuisson) sont adéquats pour contrôler la Map dans les produits de viande.
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Plamondon, Éveline. "Thermorésistance de Mycobacterium avium ssp. paratuberculosis dans les produits de la viande." Master's thesis, Université Laval, 2009. http://hdl.handle.net/20.500.11794/21031.
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Mycobacterium avium ssp. paratuberculosis (Map) est responsable de la maladie de Johne chez les ruminants en particulier chez le bovin. Les scientifiques ont émis l'hypothèse que Map pourrait être l'agent étiologique de la maladie de Crohn chez l'humain, ce qui a soulevé des inquiétudes en santé publique. Map est particulièrement résistant à la chaleur dans le lait, mais l'état des connaissances est pratiquement limité dans les matrices de viande. Les valeurs D (temps de réduction décimal) et z (sensibilité à la température) ont été déterminées dans du boeuf haché préparé aseptiquement à partir du muscle semi membranosus pour Map, Escherichia coli et Enterococcus faecalis. L'objectif de ce travail est de déterminer l'effet de divers traitements thermiques sur la cinétique de destruction de Map dans la viande afin d'évaluer si les procédés thermiques industriels (la pasteurisation, cuisson) sont adéquats pour contrôler la Map dans les produits de viande.
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Naugle, Alecia Larew. "Epidemiologic investigations of mycobacterium avium subspecies paratuberculosis infections in Ohio dairy herds." The Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054053574.
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Kühnel, Mark Philipp. "Biology of mycobacteria containing phagosomes acidification, fusion and actin nucleation ; with an emphasis on Mycobacterium avium subspecies paratuberculosis /." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=966096770.
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ALBUQUERQUE, Pedro Paulo Feitosa de. "Detecção do Mycobacterium avium subespécie paratuberculosis em amostras de leite de bovinos na microrregião de Garanhuns, Pernambuco." Universidade Federal Rural de Pernambuco, 2014. http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/5062.
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Previous issue date: 2014-02-25<br>Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES<br>The aim of the present study was to detect the IS900 region of MAP in bovine milk samples using the Real Time Polymerase Chain Reaction (qPCR) and conventional PCR, as well as to study the agreement between the tests used. In total, 121 bovine milk samples were collected from properties considered as a focus of MAP in the micro-region of Garanhuns, Pernambuco, Brazil. Of the 121 milk samples analyzed, it was possible to detect the DNA of MAP in 20 samples (16.52%) using conventional PCR and in 34 samples (28.09%) using qPCR. The DNA of the agent was detected on all of the six properties studied, ranging from 10.00% to 23.81% in the conventional PCR and from 10.00% to 36.84% in the qPCR. The agreement between qPCR and conventional PCR was moderate (Kappa =0.53; χ2 = 38.08; p<0.000). The sensitivity and specificity of conventional PCR in relation to qPCR was 50% and 96.6%, respectively. Based on these results, it was possible to conclude that the IS900 region of MAP is present in bovine milk in the micro-region of Garanhuns, Pernambuco. It was also possible to conclude that the qPCR technique used in the present study was more sensitive than conventional PCR in terms of detecting these bacteria in milk samples.<br>Objetivou-se com este estudo detectar a região IS900 do MAP em amostras de leite bovino utilizando-se as técnicas de Reação em Cadeia da Polimerase em Tempo Real (qPCR) e a PCR convencional, e realizar um estudo de concordância entre os testes utilizados. Foram coletadas 121 amostras de leite bovino de propriedades consideradas foco para o MAP pertencentes à microrregião de Garanhuns, Pernambuco, Brasil. Das 121 amostras de leite analisadas foi possível detectar o DNA do MAP em 20 (16,52%) amostras na PCR convencional e em 34 (28,09%) na qPCR. O DNA do agente foi detectado em todas as seis propriedades estudadas, variando de 10,00% a 23,81% na PCR convencional e de 10,00% a 36,84% na qPCR. A concordância entre a qPCR e PCR foi moderada (Kappa =0,53; χ2 = 38,08; p<0,000) e a sensibilidade e especificidade da PCR convencional com relação a qPCR foi de 50% e 96,6%, respectivamente. Conclui-se que o DNA da região IS900 do MAP está presente no leite bovino na região estudada e que a qPCR é uma técnica sensível e rápida para detecção desse agente em amostras de leite.
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Creignou-Mercier, Pascale. "Bases épidémiologiques pour la maîtrise de la paratuberculose caprine." Rennes 1, 2010. http://www.theses.fr/2010REN1S110.
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L’objectif était de produire des connaissances épidémiologiques descriptives pour la conception ultérieure de plans de maîtrise de l’infection des caprins par Mycobacterium avium subspecies paratuberculosis. Une enquête sérologique a permis de confirmer que l’infection par Map était très répandue dans les troupeaux caprins français, avec une prévalence vraie estimée à 63%. La détection des animaux infectés peut être réalisée par un test ELISA, dont la sensibilité et la spécificité ont été estimées à respectivement 53 et 100%. Mais les qualités des tests varient en fonction de l’âge des animaux et les meilleures valeurs ont été obtenues pour les tests ELISA sur des animaux de 2-3 ans. Pour la détection des animaux excréteurs, la PCR est le test le plus précoce (à partir de 8 mois). Comparé à la détection des animaux par PCR, le test de dosage de l’IFNγ a une sensibilité estimée à 49% et le test ELISA a une sensibilité estimée à 29%. Les apports et limites des résultats produits sont discutés dans la perspective de l’élaboration ultérieure d’actions de maîtrise et des perspectives de recherche complémentaires sont avancées<br>This study aimed at providing descriptive epidemiological knowledge about the infection of goats by Mycobacterium avium subspecies paratuberculosis, in order to design control schemes. A serological study confirmed that Map infection was widespread in goat herds in France (true prevalence estimated to 63%). Detection of infected animals can be made by ELISA, with a sensitivity of 53% and a specificity of 100%. Best values for ELISA tests were obtained for goats aged 2-3 years. For detection of infectious animals, PCR was the earliest test (from 8 months of age). With PCR as reference test, sensitivities for IFNγ test and ELISA test were estimated to 49 and 29%, respectively. Specificities for the 2 tests were estimated to 100%. Lastly, results are discussed in the perspective of the implementation of infection control schemes and further research topics are proposed
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Gollnick, Nicole Severine. "Survival of different Mycobacterium avium subsp. paratuberculosis strains in bovine monocyte-derived macrophages." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-86923.
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Robbe-Austerman, Suelee. "Evaluation of cell mediated immune diagnostic tests to detect Mycobacterium avium subspecies paratuberculosis." [Ames, Iowa : Iowa State University], 2007.
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Weigoldt, Mathias [Verfasser]. "Antigen expression and metabolism of Mycobacterium avium subsp. paratuberculosis in vivo / Mathias Weigoldt." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2012. http://d-nb.info/1036626369/34.
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Pfeiffer, Adrian [Verfasser]. "Nachweis von Mycobacterium avium ssp. paratuberculosis bei Rindern in unterschiedlichem Alter / Adrian Pfeiffer." Gießen : Universitätsbibliothek, 2017. http://d-nb.info/1132510430/34.
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O'Brien, Lorna. "Novel detection methods for Mycobacterium avium subsp. paratuberculosis : development, optimisation and field validation." Thesis, Queen's University Belfast, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709844.
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Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, a wasting disease that largely affects domestic ruminants such as cattle, sheep and goats. Clinical disease can take up to 5 years to manifest, and therefore identification of subclinically-infected animals (i.e. those which are MAP-infected but are without symptoms) is challenging. Current diagnostic approaches lack detection sensitivity and speed of acquisition of results, so there is an urgent need for the development of a rapid test, which is highly specific and highly sensitive for the detection of viable MAP in naturally-contaminated samples. The peptide-mediated magnetic separation (PMS) phage amplification assay may represent such a test as it allows for the detection of viable MAP cells within 72 hours and has an analytical sensitivity and specificity of >85% and >99%, respectively (Foddai et al., 2010). The primary objective of this research project was to optimise the PMS-phage assay further, through the generation and evaluation of novel MAP binders. Two different MS protocols were successfully developed: (1) a new PMS assay and (2) an immuno-magnetic separation (IMS) assay. Subsequently, the diagnostic potential of each of these MS protocols was evaluated, with the PMS assay successfully combined with a PCR endpoint detection method and the IMS successfully combined with both culture and phage amplification assays for the detection of viable MAP. In order to assess the diagnostic performance of the MS-based assays for the detection of viable MAP from naturally-contaminated bovine milk samples, MS-culture and MS-phage assays were employed. The results generated were compared with those of current diagnostic approaches (faecal culture and serum ELISA). Additionally, an attempt was made to characterise the binding sites of the two novel monoclonal antibodies and the peptide binder by mimotope and computational analysis. Furthermore, an alternative diagnostic application for the novel MAP-specific binders was explored through early-stage experiments to develop a lateral flow immunochromatographic assay for the detection of whole MAP cells.
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Salem, Mohamed. "Detection of Mycobacterium avium subspecies paratuberculosis in dairy herds and comparative molecular characterization." Giessen VVB Laufersweiler, 2009. http://d-nb.info/1000205576/04.
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Braga, Isis de Freitas Espeschit. "Mycobacterium avium ssp. paratuberculosis (MAP): Identificação água e fatores de risco para a presença em amostras de biópsias intestinais." Universidade Federal de Viçosa, 2015. http://www.locus.ufv.br/handle/123456789/6739.
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Previous issue date: 2015-02-20<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior<br>Mycobacterium avium ssp. paratuberculosis (MAP) é o agente etiológico da doença de Johne ou paratuberculose, enterite granulomatosa crônica caracterizada por diarreia persistente e perda de peso progressiva que acomete ruminantes. Pode também ser isolado a partir de amostras intestinais de pacientes humanos, com doenças intestinais, principalmente portadores da doença de Crohn. Essa é uma doença de etiologia desconhecida, que se caracteriza por inflamação crônica, focal, assimétrica transmural e ocasionalmente granuloma- tosa, que pode acometer qualquer segmento do tubo digestivo. O isolamento de MAP e as semelhanças entre os processos clínicos e histopatológicos da paratuberculose e da doença de Crohn são algumas das razões pelas quais se investiga o potencial zoonótico da bactéria. As principais vias de eliminação do agente são através do leite e das fezes que contaminam os pastos e, direta ou indiretamente os cursos d’agua podendo dessa forma infectar humanos pela ingestão de água contendo o micro-organismo viável. MAP é uma bactéria resistente e responsável por grandes prejuízos econômicos e produtivos, sendo demonstrada sua sobrevivência no ambiente por longos períodos, além da resistência a pasteurização e à agentes de desinfecção aplicados ao tratamento da água para consumo humano. Diante disso, o estudo teve como objetivos: - identificar fatores de risco envolvidos com a presença de MAP em amostras de intestino humano, através da aplicação de questionário, em conjunto com da- dos prévios sobre a presença da bactéria em amostras de biópsias intestinais de pacientes portadores de Doença de Crohn, retocolite ulcerativa e portadores de doenças intestinais não inflamatórias, -verificar a presença do agente na água para consumo humano e animal através de PCR convencional e do cultivo microbiológico de amostras coletados em 10 propriedades de caprinocultura leiteira da Zona da Mata Mineira e realizar uma revisão bibliográfica dos estudos sobre a paratuberculose na América Latina. Quanto às amostras de água, MAP foi identificado viável em quatro (40%) das amostras de consumo animal, e identificado por PCR em três (30%) das de consumo humano além de uma quinta amostra de consumo animal (10%). Esse resultado demonstra o papel da água como reservatório do agente, mantendo o ciclo de infecção ativo e servindo de amostra confiável para o diagnóstico da presença do agente no rebanho já que, aparentemente não está condicionada a eliminação intermitente, como ocorre com as fezes desses animais. Nesse estudo também puderam ser identificados fatores de risco para a ocorrência do agente na água e em biópsias intestinais humanas, como o consumo de leite e derivados informais, assim como histórico familiar de agravos intestinais. Na América Latina MAP foi pesquisado em 10 países e identificado em nove, infectando, bovinos, caprinos e animais silvestres. Os resultados desse estudo contribuem para a identificação de fatores de risco envolvidos na transmissão de MAP para humanos, permitindo a sugestão de medidas que previnam ou reduzam a exposição ao agente. Esses fatores de risco identificados também demonstram a importância do leite na veiculação do agente por leite e produtos lácteos, com destaque para aqueles que não passaram pela pasteurização. Além disso, os estudos sobre água auxiliaram a elucidação do papel da ingestão da água na transmissão do agente, que não é pesquisado na rotina de tratamento, indicando exposição ao agente para humanos pode ser dar através do consumo de água contaminada por fezes de animais com paratuberculose. Esse estudo foi o primeiro sobre o agente na água no Brasil, e um dos poucos no mundo.<br>Mycobacterium avium ssp. paratuberculosis (MAP) is the etiologic agent of Johne's disease or paratuberculosis, a chronic granulomatous enteritis characterized by persistent diarrhea and progressive weight loss that may affects ruminants. MAP is also be isolated from intestinal samples from human patients with intestinal diseases, particularly Crohn's disease patients. This is a disease of unknown etiology that is characterized by chronic inflammation, focal, transmural asymmetric and occasionally granulomatous lesions, which can affect any segment of the digestive tract. The isolation of MAP and the similarities between the clinical and pathologic processes of paratuberculosis and Crohn's disease are some of the reasons for investigating the zoonotic potential of bacteria. The main agent’s disposal routes are through feces and milk that contaminate pastures and directly or indirectly the watercourses and can thus infect humans by drinking water containing viable microorganism. MAP is a resistant bacteria and responsible for significant economic and productive loss, and demonstrated its survival in the environment for long periods, in addition to the resistance to pasteurization and disinfection agents applied to water treatment for human consumption. Thus, the study aimed to: - identify risk factors involved with the presence of MAP in human gut samples, through the questionnaire, together with previous data on the presence of bacteria in samples of intestinal biopsies of patients Crohn's disease, ulcerative colitis and patients with non- inflammatory intestinal diseases, -check the agent's presence in the water for human and animal consumption by conventional PCR and microbiological culture samples collected in 10 properties of dairy goat of the Zona da Mata Mineira and,- conduct a literature review of the studies on paratuberculosis in Latin America. As for the water samples, MAP was identified feasible in four (40%) of the samples of animal feed, and identified by PCR in three (30%) of human consumption as well as a fifth sample of animal consumption (10%). This result demonstrates the role of water as an agent of the reservoir, keeping the active infection cycle and serving as a reliable sample for the diagnosis of the agent's presence in the herd since apparently is not subject to intermittent shedding, as with the feces of these animals. In this study could also be identified risk factors for the occurrence of the agent in in human intestinal biopsies, as the consumption of unpasteurized milk and informal derivatives as well as family history of bowel diseases. In Latin America MAP was investigated in 10 countries and identified in nine, infecting, cattle, goats and wild animals. The results of this study contribute to the identification of risk factors involved in the MAP transmission to humans, allowing the suggestion of measures to prevent or reduce exposure. These identified risk factors also demonstrate the importance of milk in placement agent for milk and milk products, especially those who have not gone through the pasteurization. Furthermore, studies on water helped to elucidate the role of water ingestion in the transmission of the agent, which is not searched in routine treatment, indicating exposure to the agent for humans can occur through the consumption of water contaminated by faeces of animals carrying paratuberculosis. This study was the first about the agent in water in Brazil, and one of the few in the world.
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Walter, Gudrun [Verfasser]. "Differenzielle Zytokinantwort bei Ziegen nach experimenteller Infektion mit Mycobacterium avium subsp. paratuberculosis / Gudrun Walter." Gießen : Universitätsbibliothek, 2017. http://d-nb.info/113856592X/34.
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Suwandi, Abdulhadi [Verfasser], and Gerhard [Akademischer Betreuer] Groß. "Correlation between Mycobacterium avium ssp. paratuberculosis infection and colitis / Abdulhadi Suwandi ; Betreuer: Gerhard Groß." Braunschweig : Technische Universität Braunschweig, 2013. http://d-nb.info/1175821756/34.
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Spinelli, Natalia. "Characterization of posttranslational modification of 19 kDa protein expressed by Mycobacterium avium subspecies paratuberculosis." Honors in the Major Thesis, University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1142.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.<br>Bachelors<br>Burnett College of Biomedical Sciences<br>Molecular Biology and Microbiology