Дисертації з теми "Mycobacterium tuberculosis σ Factors"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-41 дисертацій для дослідження на тему "Mycobacterium tuberculosis σ Factors".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Moses, Lorraine. "Phenotypic factors influencing Mycobacterium tuberculosis phenotype." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/52997.
Повний текст джерелаDavies, Angharad Puw. "A study of resuscitation-promoting factors in Mycobacterium tuberculosis." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445460/.
Повний текст джерелаHanekom, Madeleine. "The molecular epidemiology of Mycobacterium tuberculosis : host and bacterial factors perpetuating the epidemic." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/4821.
Повний текст джерелаDissertation presented for the degree of Doctor of Philosophy at Stellenbosch University.
ENGLISH ABSTRACT: This study describes the molecular epidemiology of Mycobacterium tuberculosis strains with the Beijing genotype. This genotype has received clinical prominence due to its global distribution and the hypothesis that these strains have acquired the ability to evade the protective effect of BCG vaccination, spread more readily, acquire drug resistance and cause severe forms of disease. Molecular biological techniques were used in a series of studies to elucidate the genetic evolutionary mechanisms underlying the success of this genotype in Cape Town, South Africa. Using a collection of 40 different markers it was possible for the first time to construct a phylogenetic history of Beijing genotype strains. This phylogeny was characterized by the consecutive evolution of 7 sublineages. Analysis of epidemiological data in relation to these sublineages showed an association between more recently evolved Beijing strains and an increased ability to transmit and cause disease. From these findings it was hypothesized that the pathogenic characteristics of the Beijing genotype were not conserved but rather that strains representative of the different sublineages had evolved unique properties. In order to determine whether these socalled unique properties were associated with either the host population or the genetic background of strains from sublineage 7, a meta-analysis of published Mycobacterial Interspersed Repetitive-Unit (MIRU) typing data (East Asia) was compared with MIRU typing data from the South African strains in the context of their phylogenetic histories. This study showed that Beijing genotype strains in South Africa originated in East Asia following their introduction during the early 18th century. A significant association was observed between the frequency of occurrence of strains from defined Beijing sublineages and the human population from whom they were cultured (p <0.0001). Based on these findings it was proposed that either the host population (South African) had selected for a particular Beijing sublineage (i.e. sublineage 7) or that strains from that sublineage had adapted to be more successful in the South African population. In a subsequent study, using the methodology developed in the above studies, it was shown that strains from the ancestrally positioned lineage (termed “atypical” Beijing genotype) were over-represented in drug resistant isolates in the Eastern Cape region. This contradicts current dogma which suggests that “atypical” Beijing genotype strains are attenuated in their ability to transmit. However, this phenomenon may be ameliorated in immune-compromised patients as review of the clinical records showed that transmission was associated with HIV co-infection. These findings highlight the need to improve tuberculosis control in vulnerable populations as strains which would normally not contribute significantly to the epidemic now become a cause for concern especially if they are associated with drug resistance. To improve our understanding of the evolution of the Beijing genotype, the genomic stability of an additional 27 polymorphic markers were analysed. These markers have recently been proposed as the new standard in molecular epidemiological studies and were based on MIRU-Variable Number Tandem-Repeats (VNTR) sequences. Superimposition of the MIRU-VNTR data onto the phylogenetic tree showed excellent concordance thereby demonstrating that these alleles were largely stable over time. It is currently not known how the alleles that do change could influence pathogenicity. The results of this study also demonstrated discordance between strains defined by IS6110 DNA fingerprinting and those defined by MIRU-VNTR typing thereby demonstrating that these markers evolve independently and at different rates. Furthermore, the MIRU-VNTR typing method was unable to predict transmission of drug resistant strains which contradict previous reports from low incidence settings. This has significant implications for the use of this typing method in high incidence settings. Using an improved PCR-based method it was possible for the first time, to identify the 5 most prominent phylogenetic lineages in primary cultures of adult tuberculosis patients resident in a high HIV/TB co-infection setting. The results of this study showed that 15% of the study population was infected with two or more strains and Beijing genotype strains were over-represented in these mixed infections. Furthermore, drug susceptibility tests showed that one patient was co-infected with both a drug sensitive and a drug resistant strain. Since mixed infections have been implicated in treatment failure, these findings demonstrate the epidemiological importance of detecting mixed infections in vulnerable populations. This PCR-based method was further applied to cultures of paediatric tuberculosis patients to classify strains which spoligotyping was unable to define. The result of this study showed three mixed infections which otherwise would have been missed. In order to determine whether clinical disease presentation of patients infected with strains of the Beijing genotype were different from that of patients infected with non-Beijing genotype strains, clinical and demographic data of these two groups were analysed. This study showed that patients infected with strains of the Beijing genotype were highly infectious as defined by the increased bacterial load in sputum specimens. However, this finding could not be validated by lung pathology according to chest radiographs of infected patients.
AFRIKAANSE OPSOMMING: Hierdie studie beskryf die molekulêre epidemiologie van Mycobacterium tuberculosis rasse met die Beijing genotipe. Hierdie genotipe is van groot kliniese belang weens hul globale verspreiding en die hipotese dat hierdie rasse die vermoë ontwikkel het om die beskermende effek van BCG vaksinasie te vermy, om meer geredelik te versprei, middelweerstandigheid te ontwikkel en erger vorms van siekte te veroorsaak. Molekulêre biologiese tegnieke is gebruik in ‘n reeks studies om die genetiese evolusionêre meganismes onderliggend tot die sukses van hierdie genotipe in Kaapstad, Suid-Afrika te verklaar. Deur ‘n versameling van 40 verskillende merkers te gebruik, was dit moontlik om vir die eerste keer ‘n filogenetiese stamboom van die Beijing ras genotipe te skep. Hierdie filogenie word gekenmerk deur die opeenvolgende evolusie van 7 ras sublyne. Met die analise van epidemiologiese data in verhouding tot hierdie ras sublyne, is ‘n assosiasie tussen die mees onlangs ontwikkelde Beijing rasse en die verhoogde vermoë om te versprei en siekte te veroorsaak, getoon. Vanweë hierdie bevindinge, is ‘n hipotese daargestel dat die patogeniese kenmerke van die Beijing genotipe nie in alle raslyne voorkom nie, maar eerder dat verteenwoordigende rasse van die verskillende sublyne unieke eienskappe deur evolusie ontwikkel het. ‘n Metaanalise van gepubliseerde MIRU tipering data van Oos-Asië is vergelyk met MIRU tipering data van Suid-Afrikaanse rasse in die konteks van hul filogenetiese geskiedenis om te bepaal watter van hierdie sogenoemde unieke eienskappe geassosieer is met die gasheerpopulasie en watter eienskappe geassosieer is met die genetiese agtergrond van die sublyn 7 rasse. Hierdie studie het getoon dat die Beijing ras genotipe van Suid-Afrika hul oorsprong gekry het van Oos-Asië en vir die eerste keer waargeneem is in die vroeë 18de eeu. ‘n Betekenisvolle assosiasie is waargeneem tussen die frekwensie waarteen die rasse van ‘n bepaalde Beijing sublyn voorkom en die menslike populasie van wie hulle geïsoleer is (p < 0.0001). Gebaseer op hierdie bevindinge is dit voorgestel dat die menslike populasie (Suid-Afrikaners) vir ‘n spesifieke Beijing sublyn geselekteer het (bv. Sublyn 7) of dat rasse van hierdie sublyn aangepas het om meer suksesvol te wees in die Suid-Afrikaanse populasie In ‘n daaropvolgende studie is, deur gebruik te maak van die metodiek wat ontwikkel is vir die bogenoemde studies, getoon dat die voorouerlike sublyn (bekend as die“atipiese” Beijing genotipe) die mees verteenwoordigende sublyn was onder middelweerstandige isolate van die Oos-Kaap gebied. Dit is teenstrydig met die bestaande dogma wat bepaal dat die “atipiese” Beijing genotipe rasse hulle vermoë om te versprei verloor het. Hierdie verskynsel kan egter versterk word in immuun inkompetente pasiënte aangesien hersiening van die kliniese rekords aangedui het dat verspreiding geassosieer was met HIV ko-infeksie. Hierdie bevindinge bring die behoefte om TB beheer in vatbare populasies te verbeter, na vore, omrede rasse wat gewoonlik `n onbetekenisvolle bydrae tot die epidemie lewer, nou ‘n rede vir kommer is veral as hulle met middelweerstandigheid geassosieer is. Om ons insig rakende die evolusie van die Beijing genotipe te verbeter, is die genomiese stabiliteit van ‘n addisionele 27 polimorfiese merkers geanaliseer. Daar is onlangs voorgestel dat hierdie merkers, wat gebaseer is op MIRU-VNTR volgordes,die nuwe standaard vir molekulêre studies is. Die MIRU-VNTR data is op die filogenetiese boom geplaas en het uitstekende ooreenstemming getoon wat die allele se stabiliteit oor tyd gedemonstreer het. Dit is tans nie duidelik hoe van die allele wat wel verander, die patogenisiteit beïnvloed nie. Die resultate van die studie wys ook onenigheid tussen rasse wat deur IS6110 DNA tipering gedefinieer is en dié wat deur MIRU-VNTR tipering gedefinieer is. Dit impliseer dus dat die evolusie van merkers onafhanklik van mekaar plaasvind en teen verskillende tempos. Verder was die MIRU-VNTR tipering metode nie in staat om verspreiding van middelweerstandige rasse te voorspel nie, wat teenstrydig is met vorige verslae waar lae insidensie omgewings bestudeer is. Dit het noemenswaardige implikasies vir die gebruik van hierdie tipering metode in hoë insidensie omgewings. ‘n Verbeterde PKR-gebaseerde metode is vir die eerste keer gebruik om die 5 mees prominente filogenetiese sublyne in primêre kulture van volwasse tuberkulose pasiënte van ‘n hoë MIV/TB ko-infeksie omgewing, te identifiseer. Die resultate van hierdie studie het gewys dat 15% van die studiepopulasie geïnfekteer is met twee of meer rasse en dat die Beijing genotipe ras die meeste voorgekom het in gemengde infeksies. Verder het middelweerstandige toetse gewys dat een pasiënt geïnfekteer was met beide ‘n middelsensitiewe en ‘n middelweerstandige ras. Gemengde infeksies is al vantevore gekoppel aan onsuksesvolle behandeling en dus demonstreer hierdie bevindinge die epidemiologiese belang van die opsporing van gemengde infeksies in vatbare populasies. Hierdie PKR-gebaseerde metode is verder gebruik om rasse wat voorkom in kulture van pediatriese pasiënte, wat spoligotipering nie kon klassifiseer nie, te klassifiseer. Die resultate het drie gemengde infeksies gewys wat sonder die PKR-gebaseerde metode, nie geïdentifiseer sou gewees het. Om te bepaal of die kliniese beeld van pasiënte wat geïnfekteer is met rasse van die Beijing genotipe verskil van dié van pasiënte wat geïnfekteer is met rasse van die nie-Beijing genotipe, is die kliniese en demografiese data van die twee groepe pasiënte geanaliseer. Hierdie studie wys dat pasiënte wat geïnfekteer is met rasse van die Beijing genotipe hoogs aansteeklik is (gedefinieer op grond van hoë bakteriële lading in sputum monsters). Hierdie bevindinge kon egter nie met behulp van long patologie op borskas X-strale bevestig word nie.
Tanina, ABDALKARIM. "Structural analysis of transcription factors involved in Mycobacterium tuberculosis mycolic acid biosynthesis." Doctoral thesis, Universite Libre de Bruxelles, 2020. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/309485.
Повний текст джерелаDoctorat en Sciences biomédicales et pharmaceutiques (Pharmacie)
info:eu-repo/semantics/nonPublished
AlcÃntara, Cid Carlos Soares de. "Fatores associados ao diagnÃstico de tuberculose pulmonar entre suspeitos da doenÃa na rotina de unidades de saÃde de Fortaleza, CE." Universidade Federal do CearÃ, 2010. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=5815.
Повний текст джерелаTuberculosis (TB) is a disease that has challenged mankind since antiquity. It was believed that with the new technology, infectious diseases would be easily tracked and banned. The reality has been presented differently, despite advances in knowledge of tuberculosis and technology available for its control, the current picture is far from the targets set by governments. It is essential to the study of factors associated with pulmonary tuberculosis, since they are present in the prime-infeccÃÃo in relapse and multi-drug resistant pulmonary TB. Knowledge of data related to TB in the general population and specific groups at risk for TB are crucial to assess the epidemiological reality of our environment allowing proper organization of prevention and care activities. OBJECTIVE: To investigate factors associated with the diagnosis of TB, the frequency and characteristics of pulmonary tuberculosis with respiratory symptoms in three routine health services in Fortaleza. Cross-sectional study of quantitative accomplished through the application of a questionnaire in patients from three health units of Fortaleza. Respondents were divided on outcome of patients with tuberculosis and non tuberculosis outcome. We studied the influence of sociodemographic factors, housing conditions, behavioral factors, antecedents related to TB infection and clinical outcome for tuberculosis. RESULTS: The rate of pulmonary TB patients with respiratory symptoms among the study sample was 41.2%, but this data can not be extrapolated, the socio demographic and clinical outcome independently associated with TB were cough, fever and weight loss considering the level of six percent of significance. The main method used to assist diagnosis of TB in patients suspected of units studied in Fortaleza was the chest radiograph. The susceptibility profile of Mycobacterium tuberculosis showed 8.82 percent of MDR strains and sensitivity to isoniazid, rifampin, ethambutol and streptomycin from 88.23 percent in the samples taken and can not be extrapolated. If all TSA excluded from the hospital and found only Messejana TSA health posts, the resistance value reduces to a case of MDR 28 to TSA made, representing 3.6% of the sample, most patients with pulmonary TB had AFB positive only a cross, which may mean duration of disease not so long.
Crossman, David K. "Characterization of a novel acetyltransferase found only in pathogenic strains of Mycobacterium tuberculosis." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2007r/crossman.pdf.
Повний текст джерелаKocabas, Evren. "Identification of native co-factors of MshB and MCA from Mycobacterium species." Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/44457.
Повний текст джерелаMaster of Science
Dupont, Maeva. "Identification of novel factors involved in the exacerbation of HIV-1 infection and spread among macrophages in the tuberculosis context." Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30211.
Повний текст джерелаMycobacterium tuberculosis (Mtb), the bacteria causing tuberculosis (TB), and the human immunodeficiency virus type 1 (HIV-1), the etiological agent of acquired immunodeficiency syndrome (AIDS), act in synergy to exacerbate the progression of each other in co-infected patients. While clinical evidence reveals a frequent increase of the viral load at co-infected anatomical sites, the mechanisms explaining how Mtb favours HIV-1 progression remain insufficiently understood. Macrophages are the main target for Mtb. Their infection by the bacilli likely shapes the microenvironment that favours HIV-1 infection and replication at sites of co-infection. To address this issue, I took advantage of an in vitro model mimicking the TB-associated microenvironment (cmMTB, "conditioned media of Mtb-infected macrophages") previously established in the laboratory; a model that renders macrophages susceptible to intracellular pathogens like Mtb. Upon joining the team, I participated in the study on how Mtb exacerbates HIV-1 replication in macrophages, using this model. We found that cmMTB-treated macrophages (M(cmMTB)) have an enhanced ability to form intercellular membrane bridges called tunneling nanotubes (TNT), which increase the capacity of the virus to transfer from one macrophage to another, leading to the exacerbation of HIV-1 production and spread. The principal objective of my PhD thesis was to identify novel factors that are involved in the exacerbation of HIV-1 replication in macrophages in the context of tuberculosis. To this end, a transcriptomic analysis of M(cmMTB) was conducted, and revealed two key factors: the Siglec-1 receptor and type I interferon (IFN-I)/STAT1 signaling. The first part of my PhD thesis dealt with the characterization of Siglec-1 as a novel factor involved in the synergy between Mtb and HIV-1 in macrophages. First, I demonstrated that its increased expression in M(cmMTB) was dependent on IFN-I. Second, in Mtb and simian immunodeficiency virus co-infected non-human primates, I established a positive correlation between the abundance of Siglec-1+ alveolar macrophages and the pathology, associated with the activation of the IFN-I/STAT-1 pathway. [...]
Bortoluzzi, Alessio. "Structural characterization of Mycobacterium tuberculosis RNA polymerase binding protein A (RbpA) and its interactions with sigma factors." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/28401.
Повний текст джерелаMolino, Lucilia Pereira Dutra. "Infecção latente por Mycobacterium tuberculosis entre contatos de pacientes com tuberculose pulmonar cavitária e não cavitária." Universidade Federal do Espírito Santo, 2009. http://repositorio.ufes.br/handle/10/5917.
Повний текст джерелаThe tuberculosis continues to represent a severe worldwide public health issue, particularly in developing countries. Besides early diagnosis and therapy, one of the great challenges for its control is the scarce knowledge available about the transmission mechanisms and the related risks. The retrospective cohort described in this study aims to evaluate the risk of Mycobacterium tuberculosis infection, measured by tuberculin skin testing, in contacts of patients with cavitary and noncavitary pulmonary tuberculosis. Identification and screening of index cases between july/2003 and december/2007 was performed based on analysis of two databases: National information system of disease notification and TB notes. Only index cases, with age above 18 years old, living at Cariacica, Serra, Vila Velha and Vitoria cities were screened. Demographic, clinical and laboratory informations of the index cases and contact informations were captured from the medical charts. Bacteriological confirmation based on mycobacterial cultures was captured from TB notes database. among the 1662 index cases identified, 320 met the inclusion criteria: 154 (48,1%) with cavitary disease (C group) and 166 (51,9%) with non-cavitary disease (NC group) based on chest xray. among these 320 index cases, 1257 contacts were identified. most cases of C and NC groups denied previous contact with tuberculosis: 70,2% and 60,1%, respectively. index cases reported cough ranging between 0 and 980 days; mean of 93,5 and median of 60 days; 25 and 75 percentis were 30 and 90 days, respectively. period of cough, which represent time of disease, was higher in the c group (p=0,01, OR 1,82, IC 95%:2,8-13,5) when the threshold was 60 days. higher number of positive sputum smear patients was observed in the C group (p <0,00, OR=5,86, IC 95%: 2,8-13,5). among the 1257 enrolled contacts, 555 (44%) were contacts of the C group and 702 (56%) of the NC group patients. both groups were similar regarding gender, age and chest xray images. however, more reactors to tuberculin skin testing (PPD ≥ 10 mm) were found among contacts of C group: 48% versus 40,6% (p= 0,009, OR1,35, IC 95% 1,07-1,7 ). Taking into account images observed in chest xray, M tuberculosis infection rate was 1,7 higher among contacts of cavitary in comparison with non-cavitary patients. After logistic regression analysis this association was statistically significant for two variables: period of cough ≥ 30 days (p=0, 0007OR=3, 20, IC 95%: 1, 5-8.6,) and positivity of sputum smears (p=0, 0039 OR=2, 47, IC 95: 1, 24-4, 81). Positivity of sputum smears was also related to the presence of cavitary disease. Index cases included in C group had 5, 86 more chance of having positive sputum smear (IC 95%: 2, 8-13, 5). Using infection prevalence rate of 30% or more as the threshold for transmission analysis, the three following variables were related to infection transmission to contacts: period of cough, cavitary disease and positive sputum smear. It was concluded that: a period of cough ≥30 days was associated with TB infection; smear positivity was associated with a higher chance of infection among contacts. The association between cavitary disease and TB infection transmission to contacts was marginally statistically significant.
Um dos principais desafios para o controle da tuberculose (TB) é ainda o pouco conhecimento disponível sobre os mecanismos intrínsecos de sua transmissão e os graus de risco associados a eles. Este estudo, uma coorte retrospectiva, teve por objetivo avaliar o risco de infecção por Mycobacterium tuberculosis, medido pela prova tuberculínica, em contatos de pacientes com tuberculose pulmonar cavitária e não cavitária. A identificação e a seleção dos casos índices foram realizadas por meio da análise de dois bancos de dados: Sistema de Informação de Agravos de Notificação (SINAN) e TB notes. O período abrangido foi de julho de 2003 a dezembro de 2007. Foram selecionados indivíduos residentes em quatro municípios da Região Metropolitana de Vitória (Cariacica, Serra, Vila Velha e Vitória). De todos os casos índices com idade superior a 18 anos notificados no SINAN, obteve-se os prontuários médicos para análise dos dados demográficos, clínicos e laboratoriais e as informações dos respectivos contatos. A confirmação bacteriológica por cultura dos pacientes foi obtida no banco de dados TB-notes. Dos 1662 casos índices identificados, 320 preencheram os critérios de inclusão do estudo 154 (48,1%) com doença cavitária (grupo C) e 166 (51,9%) sem doença cavitária (grupo NC) à radiografia do tórax. Os 320 casos índices geraram 1.257 contatos. A maioria dos casos do grupo C e NC não tinha história epidemiológica de contato prévio com a doença 70,2% e 60,1%, respectivamente. O tempo de tosse variou de 0-980 dias, com média de 93,5 dias (± 130 dias), e mediana, de 60 dias. Os percentis 25 e 75 foram, respectivamente, de 30 e 90 dias. O tempo de tosse, que, na prática, retrata o tempo de doença, foi maior nos pacientes do grupo C (p=0,01, RC 1,82, IC 95%: 1,01-3,04), quando o ponto de corte foi de 60 dias. Houve uma maior concentração de pacientes com baciloscopia positiva no grupo C, o que representa uma diferença estatisticamente significativa (p <0,00, RC=5,86, IC 95%: 2,8-13,5). Dos 1.257 contatos arrolados, 555 (44%) eram contatos do grupo C, e 702 (56%) do grupo NC. Os dois grupos de contatos foram semelhantes em relação ao gênero, idade e resultado da radiografia do tórax. Houve, entretanto, diferença na prevalência de positividade da prova tuberculínica (≥10mm), que foi maior nos contatos do grupo C: 48% versus 40,6% do grupo NC (p= 0,009, RC 1,35, IC95% 1,07-1,7). Os casos índices com doença cavitária infectaram 1,7 vezes mais seus contatos do que os casos índices sem cavidade à radiografia do tórax (IC 95%: 0.94-3.08, p=0, 061). Após análise de regressão logística essa associação mostrou-se estatisticamente significativa para as variáveis: tempo de tosse superior a 30 dias (RC=3,20, IC 95%: 1,5-8.6, p=0, 0007) e positividade da baciloscopia do escarro (RC=2,47, IC 95: 1,24-4,81 p=0, 0039). A positividade da baciloscopia do escarro também esteve associada à presença de doença cavitária. Os casos índices incluídos nessa categoria possuíam 5,86 mais chance de apresentarem exame direto do escarro positivo (IC95%: 2,8-13,5). Essas três variáveis (tempo de tosse, doença cavitária e baciloscopia positiva do escarro) estiveram relacionadas à transmissão da infecção aos contatos, quando se utilizou, como ponto de corte para análise da transmissão, a presença de infecção igual ou superior a 30% nos contatos dos respectivos casos índices. Concluímos que o tempo de tosse superior a 30 dias e a baciloscopia positiva estão fortemente associados à transmissão por M.tuberculosis. Esta associação teve significância limítrofe para doença cavitária.
Liu, Dien. "Effects of R294C mutation on expression and stability of interferon regulatory factor-8 in BXH-2 mice." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116090.
Повний текст джерелаKelly, Robert Francis. "Epidemiology of bovine tuberculosis and influence of liver fluke co-infection in Cameroon, Central Africa." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/29560.
Повний текст джерелаCarvalho, BrÃulio Matias de. "Epidemiological study and resistance patterns to the anti-tuberculosis drugs in mycobacteria and hiv co-infected patients in a reference hospital in Fortaleza, CearÃ." Universidade Federal do CearÃ, 2007. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2504.
Повний текст джерелаThe HIV infection and the tuberculosis (TB) are together the main causes of death for infectious agents in the world, being approximately 13 million people infected with both causative agents. The HIV-infected individuals show increased susceptibility for active tuberculosis, being the imunosupression caused by the virus the main risk factor for the development for active TB. This study investigated the profile of Mycobacterium tuberculosis drug resistance and evaluated the factors related to the development of TB in HIV infected patients who were treated at HSJ, which is a reference hospital in infectious diseases in Fortaleza, CearÃ, Brazil. During the period of July 2003 until June 2006, 208 patients with clinical and/or laboratorial diagnosis of micobacteriosis or tuberculosis and infection for the HIV were taken care in this hospital. The TB/HIV co-infected patients were older (average: 40 years, p= 0.0025) than the control group, being approximately 4 years older. The majority of the patients were male (80.8%, p= 0.0005) and they had shown a risk to develop TB of 43.0% greater compared to the female sex. The risk to develop the TB disease was two times higher in the patients with lower educational levels (less than eight years of schooling) and they represented 85.9% of the patients (p=0.000). The history of previous contact with TB patients and previous treatment for TB were also found to be risk factors for TB. The imunosupression level was higher in TB-HIV coinfected patients being the CD4+ lymphocytes count average of 169 cells/mm Â(p=0.000) and the viral load logarithm average of 4,36 (p=0.0013). The clinical forms most frequents were pulmonary (45.7%), extrapulmonary (28.4%) and disseminated (25.9%). Of the samples that were submitted to identification, 81.2% were M. tuberculosis and 12.8% were not M. tuberculosis. The resistance frequency to one drug and multi-resistance were the same (5.9%). Overall, these observations are important for establishing political strategies of public health to improve the conditions at the regional level.
A infecÃÃo pelo vÃrus HIV e a TB estÃo entre as principais causas de morte por agentes infecciosos no mundo, aproximadamente 13 milhÃes de pessoas estÃo infectadas com ambos agentes causadores. Os indivÃduos infectados pelo HIV apresentam susceptibilidade aumentada para tuberculose ativa, sendo a imunossupressÃo determinada pelo vÃrus o principal fator de risco para o desenvolvimento da doenÃa tuberculose. Este trabalho investigou o perfil de resistÃncia do Mycobacterium tuberculosis e os fatores epidemiolÃgicos relacionados ao desenvolvimento da doenÃa em pacientes co-infectados pelo HIV atendidos no Hospital SÃo Josà de DoenÃas Infecciosas (HSJ), o qual à referÃncia em doenÃas infecciosas em Fortaleza, Estado do CearÃ, Brasil. Foram analisados, no perÃodo de julho de 2003 atà junho de 2006, 208 pacientes com diagnÃstico clÃnico e/ou laboratorial de micobacteriose ou tuberculose e infecÃÃo pelo HIV atendidos no HSJ. Os pacientes co-infectados TB/HIV apresentavam idade superior aos pacientes do grupo controle (mÃdia de 40 anos, p= 0,0025), tendo aproximadamente 4 anos a mais. O sexo masculino apresentou maioria significante (80,8%, p= 0,0005) e teve risco 43,0% superior ao sexo feminino de desenvolver TB. O risco de adquirir TB foi duas vezes maior nos pacientes com escolaridade baixa, que representavam 85,9% dos pacientes (p=0,000). A histÃria de contato prÃvio com pacientes com TB e de tratamento prÃvio para TB foram considerados fatores de risco para TB nesta populaÃÃo. O nÃvel de imunossupressÃo foi maior nos pacientes co-infectados TBHIV com contagem mÃdia de linfÃcitos T CD4+ de 169 cels/mm (p=0,000), assim como o logaritmo da carga viral com mÃdia de 4,36 (p=0,0013). As formas clÃnicas mais freqÃentes foram: pulmonar (45,7%), extrapulmonar (28,4%) e disseminada (25,9%). Das amostras que foram realizadas identificaÃÃo, 81,2% foram identificadas como M. tuberculosis e 12,8% como nÃo M. tuberculosis. A freqÃÃncia de resistÃncia a uma droga e multi-resistÃncia foram iguais (5,9%). Esses resultados fornecem informaÃÃes importantes para o estabelecimento de estratÃgias de polÃticas de saÃde pÃblicas mais adequadas a nÃvel regional.
Alvarez, Martinez Jesus Antonio. "Role of [gamma][delta]-T cells in mycobacterial infection and inflammation /." free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcitt?p9999268.
Повний текст джерелаAndriuška, Algirdas. "Vaikų tuberkuliozės kontrolės galimybės vykdant valstybinę tuberkuliozės profilaktikos ir kontrolės 2003–2006 m. programą." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2005. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2005~D_20050610_093210-17713.
Повний текст джерелаAwah, Ndukum Julius. "Epidemiology and public health significance of bovine tuberculosis in cattle in the highlands of Cameroon." Thesis, University of Plymouth, 2012. http://hdl.handle.net/10026.1/913.
Повний текст джерелаHartman, Michelle L. "M.tb Killing by Macrophage Innate Immune Mechanisms: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/606.
Повний текст джерелаJamithireddy, Anil Kumar. "Biophysical Studies on Mycobacterium Tuberculosis σ Factor – Regulatory Protein Complexes". Thesis, 2017. http://etd.iisc.ac.in/handle/2005/4170.
Повний текст джерелаGoutam, Kapil. "Structural and Functional Studies on the Mycobacterium tuberculosis σ factor σJ". Thesis, 2017. http://etd.iisc.ac.in/handle/2005/3566.
Повний текст джерелаGoutam, Kapil. "Structural and Functional Studies on the Mycobacterium tuberculosis σ factor σJ". Thesis, 2017. http://etd.iisc.ernet.in/2005/3566.
Повний текст джерелаShukla, Jinal K. "Understanding the Regulatory Steps that Govern the Activation of Mycobacterium Tuberculosis σK". Thesis, 2013. http://etd.iisc.ac.in/handle/2005/3904.
Повний текст джерелаShukla, Jinal K. "Understanding the Regulatory Steps that Govern the Activation of Mycobacterium Tuberculosis σK". Thesis, 2013. http://etd.iisc.ernet.in/2005/3904.
Повний текст джерелаGopal, Krishan. "Structural And Biophysical Analysis Of The Regulatory Mechanism Of Mycobacterium Tuberculosis Sigma Factors." Thesis, 2009. https://etd.iisc.ac.in/handle/2005/958.
Повний текст джерелаGopal, Krishan. "Structural And Biophysical Analysis Of The Regulatory Mechanism Of Mycobacterium Tuberculosis Sigma Factors." Thesis, 2009. http://hdl.handle.net/2005/958.
Повний текст джерелаCarmo, Nuno Baltazar do 1976. "Human factors required for mycobacterium tuberculosis macrophage infection." Doctoral thesis, 2013. http://hdl.handle.net/10451/15626.
Повний текст джерелаTuberculosis is a pathological manifestation of the infection by Mycobacterium tuberculosis in humans. Facultative intracellular parasites, like M. tuberculosis, evolved mechanisms to subvert the proper functioning of their host cells to their benefit. In this thesis we token advantage of the characteristics of the fluorescent proteins to develop methodologies based on fluorimetry to quantify the macrophage internalization and the number of intracellular mycobacteria. The application of these techniques allowed: 1) to demonstrate that the GFP expressing mycobacteria may be used to test the effects of new drugs namely pyrazinoic acid esters against M. tuberculosis growth in liquid cultures. However GFP is not a good fluorophore to quantify intracellular mycobacteria. Instead we found tdTomato the election fluorophore to this purpose 2) To determine the effect of 120 genes in the host vesicular traffic during macrophage infection with M. tuberculosis. We identified 10 genes, 8 lead to a reduction and 2 an increase of macrophage M. tuberculosis burden. 3) To demonstrate that a reduction in macrophage internalization was the cause for the reduction in intracellular M. tuberculosis observed in some of the genes identified in 2) and the modulation of internalization by the microRNA miR-142-3p. Additionally, we studied the effect of Rab GTPases silencing in exosome secretion. MicroRNAs (miR) are small non-coding RNA molecules that regulate gene expression. Previous studies in our laboratory shown that miR-142-3p was up-regulated during early stages of M. tuberculosis macrophage infection. MiR142-3p binds to Wasl gene controlling the expression of N-wasp protein involved in signal transduction of membrane receptors and actin cytoskeleton. N-wasp silencing reduces M. tuberculosis internalization by macrophage. These studies demonstrate that M. tuberculosis regulates its internalization through N-Wasp. Taken together our results demonstrate the effect of specific host factors in the survival and/or internalization of M. tuberculosis by macrophages. Tuberculosis bacilli apparently modulate some of them. The development of new molecules in formulations that inhibit resistant M. tuberculosis strains is another strategy for the eradication of this pathogen from humans.
A tuberculose (TB) é a manifestação patológica da infecção do Mycobacterium tuberculosis no seu hospedeiro: os humanos. Esta doença afecta os humanos há milénios e constitui ainda um problema de saúde pública a nível global. A reemergência da TB após decadas de declínio resulta sobretudo da co-infecção com o vírus da imunodeficiência humana e do aparecimento de estirpes de M. tuberculosis resistentes aos antibióticos. O M. tuberculosis é um parasita intracelular facultativo, cujo principal nicho de sobrevivência são os macrófagos: as células do sistema imune cuja função é a destruição dos microrganismos. Após fagocitado pelo macrófago, o M. tuberculosis subverte o normal funcionamento do seu hospedeiro. Os fagossomas contendo o bacilo da tuberculose não maturam para fagolisossomas, não fundindo com endossomas tardios ou lisossomas, protegendo o bacilo dos factores microbicidas do macrófago. Apesar de o fagossoma estar bloqueado num estádio precoce da sua maturação este funde com outras vesículas do macrófago hospedeiro, fornecendo à micobactéria recursos para a sobrevivência e replicação. Em particular, multiplas publicações sugerem que diferentes proteínas do hospedeiro reguladoras do tráfego vesicular ou do citoesqueleto da actina poderão desempenhar um papel relevante na sobrevivência deste patogénio. Contudo, os mecanismos através dos quais é estabelecida esta subversão não são conhecidos. O desenvolvimento de metodologias de larga escala para triagem no estudo dos factores do hospedeiro envolvidos na infecção de macrófagos, pelo M. tuberculosis, têm sido refreados pelas características únicas desta micobactéria. A única metodologia disponível para a quantificação de micobactérias intracelulares é a contagem de unidades formadoras de colónias (UFC), uma técnica laboriosa e dispendiosa. Nesta tese aproveitamos as características das proteínas fluorescentes para desenvolvermos metodologias para a quantificação da internalização e sobrevivência de micobactérias em macrófagos e em culturas líquidas. O desenvolvimento dessas técnicas permitiu: 1) Desenvolver uma metodologia baseada nas propriedades das proteínas fluorescentes para a determinação da sobrevivência de M. tuberculosis intracelularmente em macrófagos infectados. 2) Determinar o efeito de cerca de 120 genes humanos do tráfego vesicular na carga do M. tuberculosis em macrófagos humanos. 3) Estudar o efeito dos genes validados no ponto 2) e do micro RNA mIR143-3p na internalização do M. tuberculosis por macrófagos humanos. 4) Adicionalmente foi estudado o efeito do silenciamento de Rab GTPases na secreção de exosomas. De forma a desenvolver um método alternativo ao UFC compatível com a possibilidade de rastreamento em larga escala da sobrevivência de micobactérias aproveitamo-nos das características das proteínas fluorescentes com o objectivo de monitorizar a infecção de macrófagos pelo M. tuberculosis. Numa primeira fase culturas líquidas de M. tuberculosis expressando GFP foram sujeitos à acção microbicida de vários antibióticos e determinadas as suas concentrações mínimas inibitórias por fluorimetria. Posteriormente foram utilizados vários esteres derivados do ácido pirazinóico em M. tuberculosis expressando GFP por fluorimetria tendo-se quantificado a sua actividade biológica. Todos os compostos apresentaram uma maior actividade biológica que a pirazinamida ou o ácido pirazinóico. Compostos com maior comprimento da cadeia linear do álcool e maior lipofilia estão positivamente correlacionados com a actividade biológica. Apesar de adequado para a quantificação da inibição de crescimento de M. tuberculosis em culturas líquidas, a proteína GFP não se demonstrou propicia para a quantificação de micobactérias intracelulares. A quantificação por fluorimetria de M. tuberculosis intracelulares expressando a proteína fluorescente vermelha tdTomato, demonstrou-se uma boa alternativa ao UFC. Adicionalmente, a quantificação da intensidade da fluorescência de macrófagos humanos THP-1 expressando GFP, permitiu quantificar tanto o número como a viabilidade dos macrófagos. O estabelecimento de uma metodologia de rastreamento em larga escala para a quantificação de M. tuberculosis intracelular, permitiu-nos proceder ao silenciamento sistemático de cerca de 120 genes do tráfego vesicular humano e quantificar o seu efeito na carga de M. tuberculosis em macrófagos. Os candidatos obtidos no rastreamento foram posteriormente validados quanto à sua expressão genética. Identificámos 10 genes com efeito na carga intracelular de M. tuberculosis em macrófagos, em 2 genes, foi observado um aumento e em 8 genes, uma redução da carga de M. tuberculosis em macrófagos humanos. Os candidatos foram maioritariamente proteínas Rab, proteínas reguladoras e efectoras de Rab e proteínas do tráfego vesicular não classificadas. De forma a quantificar o contributo da internalização nos resultados observados no rastreamento dos 120 genes, desenvolvemos uma metodologia baseada em citometria de fluxo. Determinamos que, para micobactérias virulentas e avirulentas, a grande maioria dos genes testados são, provavelmente, reguladores positivos da internalização. Estas observações justificaram e confirmaram alguns dos resultados obtidos no rastreamento genómico e propõem um papel activo das micobactérias na modulação da sua internalização por macrófagos humanos. De forma a validar biologicamente alguns dos candidatos, estes foram silenciados novamente e foi quantificada a carga micobacteriana em macrófagos utilizando a metodologia convencional, as unidades formadoras de colónias. Com os resultados observados ficou demonstrado que a proteína Rab7a induz um aumento da carga macrofágica de M. tuberculosis. O silenciamento de Rab34 e Sintaxina 4 induz uma redução da carga de M. tuberculosis em macrófagos humanos sendo esta redução, possivelmente devida à redução da internalização nestas células. Os micro RNAs (miR), recentemente descritos, são uma nova classe de moléculas que controlam eventos pós-transcripcionais durante a expressão genética. Os miR ligam-se a regiões especificas do RNA mensageiro (RNAm) de uma proteína bloqueando a tradução proteica e/ou levando à degradação do RNAm. Os miRs controlam selectivamente a expressão de proteínas de diferentes vias metabólicas das células. Estudos feitos no nosso laboratório demonstraram que o miR-143-3p está sobre-expresso nos estádios iniciais da infecção de M. tuberculosis em macrófagos. O miR-143-3p liga-se ao mRNA do gene Wasl controlando a expressão da proteína N-Wasp, um transdutor de receptores membranares e do citoesqueleto de actina. O silenciamento da N-Wasp reduz a internalização de M. tuberculosis pelos macrófagos. Estes resultados demonstram a regulação de N-Wasp pelo M. tuberculosis para controlar a sua internalização. Os exossomas são vesículas com um diâmetro de 30 a 100 nm que são secretadas por diversos tipos de células. Os exossomas desempenham um papel importante na sinalização entre células e em macrófagos têm um papel de apresentação de antigénios. Os exossomas secretados por macrófagos infectados por M. tuberculosis são pró-inflamatórios in vitro e in vivo. No laboratório do Dr. Amigorena foi desenvolvida uma metodologia para quantificação de exossomas através de pérolas de latex conjugadas dom CD63 e a utilização de citometria de fluxo. Em colaboração com o Dr Ostrwsky, do laboratório do Dr Amigorena, Instituto Curie, Paris, França, efectuei um rastreio de larga escala para determinação dos genes do tráfego intracelular envolvidos na secreção de exossomas em células HeLa B6H4. Nesse estudo a proteína Rab27a e Rab27b foram envolvidas na secreção de exossomas em células humanas. Era nosso objectivo determinar se tal se verificava em macrófagos humanos, no contexto da infecção do M. tuberculosis, não foi possível por razões alheias à nossa vontade. Conjuntamente os dados apresentados nesta tese demonstram o efeito de factores específicos do hospedeiro que influenciam a sobrevivência e/ou internalização do M. tuberculosis por macrófagos, alguns deles aparentemente modulados pelo bacilo da tuberculose. Em particular, os dados sugerem que o M. tuberculosis desenvolveu um mecanismo específico de invasão dos macrófagos alveolares, provavelmente, para estabelecer o seu nicho replicativo sem activar em demasia o sistema imune do hospedeiro. Estes factores do hospedeiro, e em especial as proteínas que as codificam ou regulam são potenciais alvos para o desenvolvimento de drogas orientadas para a modulação do hospedeiro de forma a inibir ou controlar a infecção por M. tuberculosis. O desenvolvimento de novas drogas em formulações que inibam estirpes de M. tuberculosis resistentes é outra estratégia de erradicação deste patogénio nos humano.
Fundação para a Ciência e a Tecnologia (FCT)
Mapela, Lusanda Thato. "Characterization of resuscitation promoting factors in Mycobacterium smegmatis." Thesis, 2012. http://hdl.handle.net/10539/11937.
Повний текст джерелаHsu, Ai-Hsi, and 胥愛璽. "The Study of Host-Related Factors in Infection of Mycobacterium tuberculosis." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/76522430679624501243.
Повний текст джерела慈濟大學
醫學科學研究所
101
The annual incidence of new pulmonary tuberculosis cases in Eastern Taiwan was significantly higher than average incidence across Taiwan. In the first chapter, the theme of the research is to explore Mycobacterium tuberculosis (Mtb) outbreaks amongst hosts. Take advantage of the molecular tools combined spoligotying and mycobacterial interspersed repetitive unit-variable tandem-repeat (MIRU-VNTR), two PCR-based techniques, we may identify Mtb genotype and explore the multi drug-resistant tuberculosis (MDRTB) transmission in Eastern Taiwan. The results showed a 61.6% cluster ratio between MDRTB infected subjects in Eastern Taiwan, especially amongst indigenous groups. MDR strains might cause widespread transmission contrasted with the previous view that MDR-TB was less infectious. In chapter 2, we intend to investigate if diabetes mellitus (DM) is correlated with the infection of drug-resistant tuberculosis strains. Also, we stratified the subjects according to their tuberculosis treatment history. The host immunity of diabetic patients may be poor compare to those without diabetes; more diabetic subjects are supposed to be re-treated for tuberculosis infection. Irrespective of new or previously treated status, DM was found to be significantly associated with isoniazid-related resistant strains of tuberculosis both in new and re-treated subjects, which showed an adjusted odd ratio: 6.76 compared to those without DM. In this retrospective investigation, we did not find the significant association between DM and MDRTB, which may be attributed to the limited sample size. In chapter 3, we animal model was utilized to investigate defense mechanism of host against tuberculosis infection via a molecular perspective. Indoleamine 2,3-dioxygenase 1 (IDO1) is as a rate limiting enzyme in tryptophan metabolism and could exert a tolerogenic function in regulating the immune system. So far, no evidence proved that IDO1 can exert a killing effect against M. tuberculosis in vivo despite the fact that IDO1 own antimicrobial property against some pathogenic microbes. In this thesis, relevant experiments were conducted majorly upon its immuno-regulatroy effect in the mice model. IDO1 interacts with regulatory T cell by a direct contact fashion and is crucial in specifying to the development of a Foxp3 positive regulatory lineage during the CD4+ T cell lineage differentiation; in addition, tryptophan metabolites were reportedly to participate in the development of Th1 and Th17 cell differentiation. The mechanisms how IDO1 gene regulate the immune homeostasis in tuberculosis infection were less documented. In our preliminary data, tuberculosis infection might lead to distinct difference in mortality between IDO1 knockout mice and their counterparts with C57BL/6 background. Thus far we have shown that enzymatic degradation of tryptophan might be restored by alternative pathways in later stage of Mtb infection in IDO1-/- mice. However, its immune modulating ability may not be replaced and contributed to the distinct mortality phenotypes. Moreover, different doses of Mtb antigens exposure might act significantly in host’s immune homeostasis, which has shown in our study to influence the mortality between IDO1-/- and WT mice. In 1600CFU Mtb CFU infection via aerosol route, there was an earlier mortality in IDO1 -/- mice; a persistent higher proportion of neutrophil influx into the lungs, which was assumed at least to be link with Th17 lineage specification and IL-17a chemo-attraction. Also, the mortality was suspected to be partially associated with the IL-10 production of neutrophils. In this study, we also investigated the IDO2 response to Mtb infection.
Pope, Steven Scott. "Roles of transcription factors, RBPA and SIGF, in the mycobacterium tuberculosis." Thesis, 2015. https://hdl.handle.net/2144/16201.
Повний текст джерелаShahbaaz, Mohd. "Computational and experimental studies of putative virulence factors of Mycobacterium tuberculosis H37Rv." Thesis, 2017. http://hdl.handle.net/10321/2661.
Повний текст джерелаIn drug discovery and development of anti-tubercular therapeutics, it is necessary to study the physiology and genetics of the molecular mechanisms present in the Mycobacterium tuberculosis. The virulence of M. tuberculosis is attributed to its unique genome, which contains a high frequency of glycine-rich proteins and genes involved in the metabolism of the fatty acids. Consequently, the presence of a diversity of the pathogenic pathways such as acid tolerance and drug resistance mechanisms in M. tuberculosis makes the treatment of Tuberculosis (TB) challenging. However, the molecular basis of the virulence factors involved in the pathogenesis is not fully understood. Accordingly, the current study focuses on better understanding of the pathogenic proteins present in this bacterium using available computational techniques. In South Africa, there is an alarming increase in the drug-resistant TB in HIV co-infected patients, which is one of the biggest challenges to the current anti-tubercular therapies. An extensive literature search showed that the mutations in the virulent proteins of M. tuberculosis resulted in the development of drug tolerance in the pathogen. The molecular and genetic studies identified frequently occurring point mutations associated with the drug resistance in proteins of M. tuberculosis. Despite the efforts, TB infection is still increasing because different pathogenic pathways in the bacterial system are still undiscovered. Therefore, this study involves an in silico approach aimed at the identification of novel drug resistance implicated point mutations. The site- directed mutations leading to the development of resistance against four first-line drugs (Ethambutol, Isoniazid, Rifampicin, and Streptomycin) were studied extensively. In the primary investigation, pathogenic mutational landscapes were classified in the sequences of the studied proteins. The effects of these mutations on the stability of the proteins were studied using diverse computational techniques. The structural basis of the point mutations with the highest destabilizing effects was analyzed using the principles of the Density Functional Theory (DFT), molecular docking and molecular dynamics (MD) simulation studies. The varied conformational behavior resulted from these predicted substitutions were compared with the experimentally derived mutations reported in the literature. The outcome of this study enabled the identification of the novel drug resistance-associated point mutations which were not previously reported. Furthermore, a detailed understanding of the conformational behavior of diverse virulent proteins present in M. tuberculosis was also generated in this study. Literature study showed that inside the host’s macrophage cells, the virulent proteins such as isocitrate lyase, lipase lipF, magnesium transporter MgtC, porin protein OmpATb, a protein of two component systems PhoP, Rv2136c and Rv3671c have an established role in the development of the acid tolerance. On the other hand, information regarding their role in the acid resistance is scarce. Accordingly, the structural basis of their role in acid resistance was analyzed using constant pH based MD simulations. In the studied proteins, the lipF and PhoP showed highest structural stability in highly acidic conditions throughout the course of MD simulations. Therefore, these proteins may play a primary role in the process of resistance. In addition to these pathogenic proteins, there is a need to identify new undiscovered virulent proteins in the genome of M. tuberculosis, which increases the efficiency of the current therapy. The knowledge generated by the analyses of the proteins involved in resistance and pathogenic mechanisms of M. tuberculosis forms the basis for the identification of new virulence factors. Therefore, an in silico protocol was used for the functional annotations and analyses of the virulence characteristics. M. tuberculosis contains 1000 Hypothetical Proteins (HPs), which are functionally uncharacterized proteins and their existence was not validated at the biochemical level. In this study, the sequences of the HPs were extensively analyzed and the functions of 662 HPs were successfully predicted. Furthermore, 483 HPs were classified in the category of the enzymes, 141 HPs were predicted to be involved in the diverse cellular mechanisms and 38 HPs may function as transporters and carriers proteins. The 307 HPs among this group of proteins were less precisely predicted because of the unavailability of the reliable functional homologs. An assessment of the virulence characteristics associated with the 1000 HPs enabled the classification of 28 virulent HPs. The structure of six HPs with highest predicted virulence score was analyzed using molecular modelling techniques. Amongst the predicted virulent HPs, the clone for Rv3906c purchased from the DNASU repository because of the ease of its availability. The gene of Rv3906c was isolated and cloned into a pET-21c expression vector. The analyses of the nucleotide sequence showed that Rv3906c gene (500 bp) encodes a 169 amino acid protein of molecular weight 17.80 kDa (~18.0 kDa). The sequence analyses of Rv3906c showed that the HPs showed high similarities with pullulanase, a thermophilic enzyme. The stability profile at different temperatures for Rv3906c generated using MD simulations showed that Rv3906c maintained its structural identity at higher temperatures. It is expected that this study will result in the design of better therapeutic against the infection of M. tuberculosis, as novel undiscovered virulence factors were classified and analyzed in addition to the conformational profiles of the virulent proteins involved in the resistance mechanisms.
M
Weng, Shang-Hui, and 翁上惠. "Bacterial Factors Involved in Mycobacterium marinum and Mycobacterium tuberculosis Type VII Secretion System Induced NLRP3 Inflammasome Activation." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/598j62.
Повний текст джерела國立臺灣大學
微生物學研究所
107
Human tuberculosis, also known as "the white plague", mainly results from Mycobacterium tuberculosis infection which was found in early human history. Due to the long incubation period and drug resistance of M. tuberculosis, the researches of diagnosis and treatment in tuberculosis still remain a considerable development space. Generally, many studies on M. tuberculosis and tuberculosis use Mycobacterium marinum with higher safety and faster growth rate as a model in laboratory works. M. marinum shows high conservation with M. tuberculosis in genetic relationship and the type seven secretion system, which is critical for virulence. In our study, first we used five constructed M. marinum ESX-1 gene deletion mutants: ∆espE, ∆espF, ∆espG, ∆espH and ∆eccA1 to investigate the role of the type seven secretion system ESX-1 in NLRP3 inflammasome activation. After infecting THP-1 differentiated macrophages with these deletion mutants respectively, we found ∆espG induced less IL-1β in cell supernatant through enzyme-linked immunosorbent assay (ELISA). Our data from Western blot also showed ∆espG reduced activated caspase-1 secretion in infected macrophages. Additionally, THP-1 cells pretreated with NLRP3 inhibitor before infected with wildtype M. marinum showed the difference in secretion of IL-1β, while ∆espG-infected cells did not show this pattern. The data could indirectly demonstrate that M. marinum induces IL-1β through activating NLRP3 inflammasomes, and espG may involve in NLRP3 inflammasome activation. Subsequently, we constructed the M. tuberculosis espG1 deletion mutant and the espG1 complemented strains, infected THP-1 cells with M. tuberculosis, and analyzed the protein expression level of IL-1β and caspase-1 in cell lysate and supernatant. Although M. tuberculosis espG1 deletion mutant reduced the secretion of IL-1β significantly, the complemented strain did not repair the function of espG1 completely. In view of the previous studies that ESAT-6 in M. tuberculosis is involved in activation of NLRP3 inflammasomes, we used Western blot to analyze whether the difference in IL-1β secretion is related to the expression of ESAT-6 in M. marinum espG and M. tuberculosis espG1. According to the results, the ESX-1 major virulent proteins, ESAT-6 and CFP-10, showed substantial decrease in both M. marinum ∆espG and M. tuberculosis ∆espG1::pMN437 supernatants respectively, but were increased in bacterial lysates. Thus, we suggested that M. marinum espG gene and M. tuberculosis espG1 gene are involved in secretion of ESAT-6 and CFP-10.
Leung, Andrea. "Genetic Factors Influencing BCG Vaccine Properties." Thesis, 2010. http://hdl.handle.net/1807/25756.
Повний текст джерелаTimóteo, Pedro Manuel Dias 1990. "Deciphering host factors for mycobacteria internalization during phagocytosis." Master's thesis, 2013. http://hdl.handle.net/10451/9472.
Повний текст джерелаA tuberculose é uma doença infecciosa que tem acompanhado historicamente a Humanidade. Caracteriza-se tipicamente por uma infecção pulmonar, manifestando-se através de tosse persistente, febre e especialmente por uma fraqueza generalizada. Apesar da sua ancestralidade, é ainda hoje a doença infecciosa responsável pelo maior número de mortes a nível mundial. O agente etiológico da tuberculose é uma bactéria, Mycobacterium tuberculosis, descrita pela primeira vez por Robert Koch no século XIX. Pertence à ordem Actinomycetales e à família das Mycobacteriaceae; são bacilos, Gram-positivos, e apresentam por norma um crescimento lento e uma membrana com uma composição invulgar, rica em lípidos particulares como o lipoarabinomanano. M. tuberculosis é um patogénio particularmente resistente por se encontrar extremamente adaptado ao hospedeiro humano, e o problema agrava-se com a actual epidemia do vírus de imunodeficiência humana (VIH). Indivíduos infectados com VIH não só têm uma probabilidade maior de desenvolver tuberculose, como apresentam morbilidades mais elevadas, sendo a tuberculose a principal causa de morte entre doentes de VIH. Outro dos obstáculos mais significativos é a resistência a antibióticos, que nas últimas décadas se tem tornado mais proeminente em M. tuberculosis. Várias ocorrências de resistência aos antibióticos de primeira e segunda linha foram já documentados, e o surgimento de estirpes multirresistentes representa um sério problema de saúde pública. Continua a não existir uma vacina eficaz para substituir a BCG (Bacilo Calmette-Guérin, estirpe atenuada do agente da tuberculose bovina Mycobacterium bovis), que está em uso desde 1921, e cuja eficácia na protecção contra a tuberculose pulmonar em adultos é manifestamente insuficiente. Muita da dificuldade em combater a tuberculose está também relacionada com a sua prevalência e persistência. Segundo a Organização Mundial de Saúde, um terço da população mundial pode ser portadora de M. tuberculosis no seu estado latente, ou seja, sem desenvolver doença activa. Ainda que a doença não seja contagiosa neste estado, a sua presença no hospedeiro pode vir a manifestar-se de forma oportunista em casos de enfraquecimento imunitário, como por VIH, drogas imunossupressivas, doença concomitante ou simplesmente pelo envelhecimento. Por estas razões a investigação no combate à tuberculose está cada vez mais a dirigirse no sentido de compreender os sistemas de imunidade do hospedeiro e a sua relação com este patogénio. A pedra angular da interacção patogénio-hospedeiro é a fagocitose. É um processo de imunidade inata altamente conservado evolutivamente através do qual células eucarióticas são capazes de internalizar e digerir partículas externas ou microorganismos, eliminandoos. Certas células do sistema imunitário humano servem-se deste processo para neutralizar patogénios invasores, denominando-se células fagocitárias, ou fagócitos, entre os quais se destacam os macrófagos. M. tuberculosis é tipicamente inalado por aerossóis e nos pulmões entra em contacto com os macrófagos alveolares residentes, que oferecem a resposta fagocitária inicial. Da fagocitose fazem parte várias etapas. Tem início pela internalização das partículas, que consiste na captura e envolvimento do alvo numa vesícula endocítica. Esta é depois transportada pelo citoplasma, via elementos do citoesqueleto, e vai fundindo com outras vesículas endocíticas. Quando o grau de maturação é compatível funde-se com lisossomas, cujo conteúdo enzimático assegura uma degradação proteolítica do alvo. A este processo dá-se o nome de biogénese do fagolisossoma, e nele inicia-se a acção de proteases denominadas catepsinas, bem como óxidos nítricos e superóxidos de efeito bactericida. Depois de digerido o conteúdo fagocitado, os antigénios resultantes serão utilizados para despoletar uma resposta imunitária adquirida, levada a cabo por células T. Quando a partícula a fagocitar é o M. tuberculosis, este é capaz de subverter os mecanismos de defesa do fagócito, conseguindo sobreviver e multiplicar-se no interior da célula hospedeira. Sendo complexo o arsenal molecular de que o fagócito dispõe para combater invasores, também o é o modo como esta micobactéria o evita. O M. tuberculosis consegue impedir a maturação do fagossoma, controlando o hospedeiro através de processos que ainda não são totalmente compreendidos. Sabe-se, porém, que influencia a função de proteínas de tráfego vesicular e transporte membranar, bem como as referidas catepsinas. Sendo estes alguns dos alvos da sua virulência, tornam-se também importantes alvos de investigação biomédica, pois podem ajudar a combater a estratégia de infecção de M. tuberculosis, fortalecendo as defesas do hospedeiro. A fase de internalização das bactérias por macrófagos é um ponto crítico na infecção, uma vez que representa um dos primeiros contactos entre o patogénio e o hospedeiro, e é através dela que têm início todos os restantes mecanismos. Interessa pois compreender como é regulada a internalização, e que influência terá M. tuberculosis nessa regulação. Para estudar devidamente factores de internalização, é necessário em primeiro lugar definir o modelo de internalização de partículas inertes para estabelecer o que ocorre na fagocitose como fenómeno abrangente. Criámos um desenho experimental que nos permitiu explorar um grande número de variáveis. Fizemos variar o tipo de micobactéria: destruída no fagócito (caso de M. smegmatis) versus sobrevivente intracelular (caso de M. tuberculosis), o tempo, a multiplicidade de infecção (MOI, representa o número de bactérias por cada macrófago) e o tipo de macrófago. Para este trabalho foram utilizados três tipos de macrófagos: macrófagos derivados de monócitos humanos (HMDM), macrófagos humanos da linha celular THP-1 e macrófagos de ratinho da linha celular J774. Utilizámos também três espécies dentro do género Mycobacterium: M. tuberculosis, M. bovis BCG e M. smegmatis, sendo as duas últimas consideradas não-patogénicas. Obtendo os valores de internalização ao longo de três pontos no tempo (30 minutos, 1 hora e 4 horas) tornou-se possível traçar perfis de internalização para cada combinação de variáveis. As estirpes à nossa disposição expressavam proteína verde fluorescente (GFP) por meio de um plasmídeo replicativo, o que permitiu que os macrófagos que internalizaram micobactérias pudessem ser identificados em citometria de fluxo através da fluorescência no comprimento de onda do verde. Armados desse desenho experimental e de um protocolo de infecção eficiente que permitiu testar várias variáveis em simultâneo, descrevemos curvas de internalização para as várias combinações de macrófago-micobactéria. Destes resultados foi possível chegar à conclusão esperada de que a internalização é fortemente influenciada pelo tempo e pela multiplicidade de infecção, ou seja, estes factores condicionam fortemente a resposta fagocitária dos macrófagos. Tornou-se também evidente que os HMDM são os agentes fagocitários mais eficientes de entre os macrófagos testados, tendo sido capazes de atingir elevados níveis de internalização mais rapidamente que os restantes. Uma observação que se nos revelou pertinente foi a de que ao fim de apenas 30 minutos, todos os tipos de macrófagos foram capazes de realizar uma considerável internalização das micobactérias na amostra. Põe-se assim em causa muito do background experimental em micobactérias, que prevê infecções de duração igual ou superior a 3 horas. Este nosso trabalho sugere que infecções mais breves são não apenas funcionais, mas até preferíveis para o estudo de reguladores das fases iniciais de fagocitose, como é o caso da internalização. Infecções demasiado prolongadas podem levar à perda desta informação e a uma alteração do estado fisiológico dos macrófagos, particularmente com cargas bacterianas elevadas. Foi também importante observar que as diferentes espécies de Mycobacterium apresentam diferenças ao nível da internalização. M. smegmatis foi internalizada mais rapidamente e em maiores quantidades, seguida por M. bovis BCG e esta por M. tuberculosis. Ora, a esta ordem de internalização corresponde a ordem de inversa de patogenicidade, ou seja, com o aumento da patogenicidade diminui a internalização. Levanta-se imediatamente a sugestão de que a diminuição da internalização será um dos processos de virulência de M. tuberculosis. Parece haver uma contradição, pois sendo M. tuberculosis um patogénio intracelular esperar-se-ia que promovesse a sua internalização o mais possível. No entanto, uma carga microbiana demasiado elevada sobre as células do hospedeiro leva a processos de morte celular, privando assim M. tuberculosis do seu habitat. Força-se então um equilíbrio cuja regulação importa compreender. Para investigar o papel de factores do hospedeiro que influenciem a internalização, realizámos uma triagem sobre 71 proteínas envolvidas em tráfego vesicular e na maturação do fagossoma, a maioria pertencente aos grupos das Rab guanosina trifosfatases (Rab GTPases), catepsinas e cistatinas. Pelo silenciamento de cada uma das proteínas individualmente torna-se possível avaliar a sua contribuição para o processo de internalização, ou seja, descobrir a sua função por redução ou ausência-de-função. O silenciamento individual das proteínas foi feito por intermédio de bibliotecas lentivirais contendo plasmídeos que codificam para um pequeno RNA de interferência (hairpin), complementar ao RNA mensageiro de um gene específico. Graças a essa complementaridade o RNA mensageiro é destruído, impedindo-se assim a produção da proteína correspondente. Assim construímos uma linha knockdown de macrófagos THP-1, a qual submetemos a ensaios semelhantes aos que desenvolvemos na primeira parte dos trabalhos. Na abordagem experimental, as variáveis de tempo e MOI foram restringidas a apenas 1 hora e uma MOI de 10, pois estes valores representam um estímulo mais moderado e permitem assim realçar as eventuais diferenças provocadas pelos silenciamentos. Utilizámos nesta fase apenas M. tuberculosis e M. smegmatis na qualidade de controlo não-patogénico. Nestas condições, a grande maioria dos silenciamentos provocou um decréscimo na internalização de micobactérias, o que levou a que as suas proteínas-alvo fossem classificadas como potenciais reguladores positivos da internalização. Aplicando limites para aquilo que deveria ser considerada uma diferença significativa face aos controlos nãosilenciados, 26 proteínas emergiram como reguladores, sendo por isso denominados os hits da triagem. Este é um número surpreendentemente elevado, tendo em conta que as bibliotecas lentivirais não foram desenhadas especificamente para ensaios de internalização. Destes hits destacam-se especialmente aqueles que se manifestaram apenas em infecções com uma das micobactérias, pois permitem inferir uma relação directa com a patogenicidade. É o caso da catepsina L, identificada como hit apenas para M. smegmatis. Considerando que a ausência desta proteína levou a que M. smegmatis fosse internalizado em menor nível e, tendo presente a correlação demonstrada entre baixa internalização e patogenicidade, pode dizer-se que nesta situação M. smegmatis se comportou como uma micobactéria patogénica. Daqui se retira que o silenciamento da expressão de catepsina L pode ser uma das vias através das quais M. tuberculosis manifesta a sua patogenicidade. Três outras proteínas demonstraram um papel regulatório na internalização apenas em infecções com M. tuberculosis: Rab37, Rab38 e catepsina W. Desta última são conhecidas funções na regulação da citotoxicidade de linfócitos, mas não é claro o seu mecanismo de acção. No caso de Rab37 e Rab38, este trabalho representa a primeira associação destas à infecção por M. tuberculosis. Tratando-se de uma triagem abrangente, só será possível definir o modo de funcionamento destas proteínas com novas experiências no futuro. Os restantes 22 hits não são menos importantes; apesar de conhecida a sua associação à tuberculose, demonstraram pela primeira vez ser reguladores positivos da internalização. Há limitações ao estudar infecções in vitro, pois as conclusões a retirar não são necessariamente igualmente válidas para o contexto real de infecções por M. tuberculosis. As diferenças acentuam-se se considerarmos que neste trabalho experimental se simulou um cenário de uma primo-infecção, ou seja, o primeiro contacto entre M. tuberculosis e células humanas, sendo este um cenário artificial que não corresponde à maioria dos casos de tuberculose em humanos. É uma concessão necessária para a investigação experimental e apesar de tudo não impede que estas descobertas tenham potencial terapêutico. As proteínas aqui identificadas poderão servir para controlar mais eficazmente a infecção, se aprofundado o conhecimento sobre a sua função. Esta tese apresenta pois uma nova abordagem experimental, na forma de infecções breves e eficientes e de novos intervenientes nos primeiros passos do equilíbrio dinâmico entre patogénio e hospedeiro.
Mycobacterium tuberculosis is a very successful pathogen that is able to survive and multiply inside the host’s immune cells, thus triggering the active disease of tuberculosis or alternatively entering into an asymptomatic latent state. Its success lies on a powerful subversion of the fundamental innate immunity process of human-host cells: phagocytosis. M. tuberculosis is known to resist destruction by phagocytes through a complex molecular sabotage of phagosome maturation, an integral part of the phagocytic process. On the other hand, internalization, the first and arguably most important step of phagocytosis, has not been so thoroughly investigated. In this work we outline a method for quantifying internalization of green fluorescent mycobacteria through flow cytometry. With it we provide profiles of internalization-over-time for J774, THP-1 and human monocyte-derived macrophages (HMDM), which were infected with M. tuberculosis, M. bovis BCG and M. smegmatis. From these experiments we gathered that HMDM are the most efficient in internalizing mycobacteria, that there is considerable internalization even after short time periods such as 30 minutes and also that M. tuberculosis is internalized to a lesser extent than its non-pathogenic counterparts. It is suggested that M. tuberculosis manipulates its own internalization. In order to decipher which are the host factors targeted by this subversive strategy, we performed an internalization-based screening on knockdown THP-1 macrophages. Protein knockdowns were achieved by shRNA interference from lentiviral libraries targeting a total of 71 proteins. Using the previously designed method, we identified 26 putative positive regulators of internalization including a large number of Rab GTPases and cathepsins, proteins associated with vesicular trafficking and proteolysis in the mature phagosome. Through this novel approach we were able to quantify rates of internalization, which were previously only empirically estimated, and use them as a model to highlight new potential therapeutic targets in the ongoing battle against tuberculosis.
"A multilevel analysis of factors associated with clustered strains of Mycobacterium tuberculosis in Louisiana." Tulane University, 2007.
Знайти повний текст джерелаNdwandwe, Duduzile Edith. "Mechanisms of mutagenesis in Mycobacterium tuberculosis: structural and functional characterisation of the DNA polymerase accessory factors encoded by Rv3394c and Rv3395c." Thesis, 2013. http://hdl.handle.net/10539/12918.
Повний текст джерелаMycobacterium tuberculosis is presented with environmental host assaults that damage its DNA during infection. Tubercle bacilli possess mechanisms to protect against moststresses imposed by the host, including genotoxic stress. However, tolerance of DNA lesions that have escaped the normal repair processes requires the function of specialist DNA polymerases that can introduce mutations during translesion synthesis (replication by-pass), thus leading to damage-induced mutagenesis. Mycobacteria employ a novel DNA polymerase, DnaE2, for DNA damage tolerance and induced mutagenesis. DnaE2 belongs to the C-family of DNA polymerases, which are known to replicate DNA with high fidelity, and has been implicated in virulence and the emergence of rifampicin resistance of M. tuberculosis in vivo. In this study, DnaE2 was shown to function in the same pathway as two accessory proteins, ImuB and ImuA’, for damage tolerance and induced mutagenesis in mycobacteria. In this system, DnaE2 performs the polymerase function in translesion synthesis whereas ImuB is a cryptic Y-family DNA polymerase that lacks critical active site residues. It contains a β-clamp binding motif that allows interaction with the β-clamp and presumably enables DnaE2 and ImuA’ to access the replication fork. ImuB has a C-terminal region extending from the β-clamp binding motif which contains disordered regions that allow the interaction with other proteins and is important for function. ImuA’ is also essential for damage tolerance and induced mutagenesis but its function remains unknown. This protein is structurally similar to Escherichia coli RecA protein in the N-terminus and the middle domain, but it has a distinct C-terminus that was shown to be important for the interaction with ImuB. The essential replicative, C-family polymerase, DnaE1, was shown to be upregulated in response to DNA damage and was also shown to interact with ImuB. To explore the possibility that other proteins are involved in this pathway, ImuB was Cterminally tagged for use as bait in pull-down experiments in M. smegmatis. However, introduction of the tag disrupted ImuB function, further reinforcing the importance of the Cterminal region of ImuB for the function of this protein, presumably via protein-protein interactions. In contrast, a variant of ImuA’ which was N-terminally tagged was shown to retain functionality; however, experiments using this protein as a bait for pull-down proved to be unsuccessful. Proteomic analysis of wild type M. smegmatis, a dnaE2 deletion mutant and complemented derivative was carried out on cells exposed to the same conditions as used in the pull-down assay. Base excision repair (BER) components were identified in this analysis, but did not detect ImuB and ImuA’, suggesting that the levels of expression of these proteins were comparatively lower under the conditions tested resulting in failure of the pull-down experiment. Finally, numerous attempts were made to express and purify recombinant forms of ImuB and ImuA’ in E. coli for use in structural studies. Both proteins were expressed in the soluble and insoluble fractions; however the levels of soluble protein were low, and as a result, purified protein preparations could not be obtained.
Wolf, Andrea J. "In vivo analysis of factors affecting the dynamics of the adaptive immune response to Mycobacterium tuberculosis and contributing to bacterial persistence." Diss., 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3289328.
Повний текст джерелаMitra, Anirban. "Insights into Occurrence and Divergence of Intrinsic Terminators and Studies on Rho-Dependent Termination in Mycobacterium Tuberculosis." Thesis, 2013. http://etd.iisc.ac.in/handle/2005/3382.
Повний текст джерелаMitra, Anirban. "Insights into Occurrence and Divergence of Intrinsic Terminators and Studies on Rho-Dependent Termination in Mycobacterium Tuberculosis." Thesis, 2013. http://etd.iisc.ernet.in/2005/3382.
Повний текст джерелаJha, Rajiv Kumar. "Insights into the Regulation of Transcription Initiation of DNA Gyrase and Role of Transcription Factor Gre from Mycobacterium tuberculosis." Thesis, 2017. https://etd.iisc.ac.in/handle/2005/4681.
Повний текст джерелаMoiane, Ivânia Cláudia. "Prevalence and risk factors of bovine tuberculosis in cattle in rural areas of Govuro district in the southeast of Mozambique." Master's thesis, 2013. http://hdl.handle.net/1822/45376.
Повний текст джерелаIn Mozambique, bovine tuberculosis (BTB) is a serious problem for livestock development; however, surveillance and control programs are not applied consistently and systematically. This disease has direct economic repercussions on livestock due to lower productivity of infected animals, as well as the increased rejection of carcasses at the slaughterhouses. Due to the direct economic repercussions and indirect consequences for human health, knowing the precise distribution of the disease throughout the country is essential to define an effective control strategy and reduce BTB incidence and spread. Although the prevalence in free-ranging wildlife species is unknown, non-systematic surveys have reported a wide variation of BTB prevalence in cattle in different regions of the country and even in distinct herds of the same region. In the Govuro district the BTB’s prevalence levels previously obtained are hardly intercomparable, ranging from 1.49% in one region, using single intradermal tuberculin test (SITT) in caudal fold, to 61.94%) in another region where the SITT was applied in the middle neck region. This latter prevalence level represents one of the highest for BTB in the country and represents a serious risk for the transmission of the disease to humans. However, it should be considered that, a positive result using SITT may be related with cross-reactivity with environmental mycobacteria. We conducted a cross-sectional study in the Govuro district in order to determine the prevalence of BTB in cattle and identify associated risk factors. To access the disease burden in the district, a representative sample of the cattle population from all livestock areas (n=14) was defined using the Epicalc 2000 statistical software (Brixton Books v.1 2); assuming an expected prevalence of 10% with a standard error precision of 0.05 (5%). To compensate for noncompliance (animals selected for tuberculin test but failing the reading day), 20% more animals were targeted at testing. A total of 1136 cattle from 289 different owners were submitted to the more accurate test, the single comparative intradermal tuberculin test (SCITT). Their body condition scores, sex, age and breed were recorded to obtain a better understanding of BTB risk factors. Data analysis was performed using a logistic regression model with binary outcome and livestock area as random effect. The overall prevalence was estimated at 39.6% [95% with confidence interval (CI): 36.8-42.5] and, with the exception of the Luido area (animals from two private farmers), BTB reactors were found in all studied areas with quite diverse prevalence rates. SCITT results showed that 137 (12%; 95% CI: 10.3-14.1) out of 1136 cattle tested reacted positive to avian PPD. From 289 cattle raisers with tested cattle, 192 (66.4%; 95% CI: 60.8- 71.6) had positive cattle. Age was found to be the main individual risk factor; animals older than 4 years were more likely to be positive reactors (45.4% vs 21.9%; OR 2.9, 95% CI: 42.1 – 49.0). Females (37.2%; OR 1.1, 95% CI: 33.9 – 40.7) and animals in good body condition (35.5%; OR 35, 95% CI: 32.0 – 39.1) were associated with lower prevalence’s, although no significant differences were found. Most of the cattle included in the present study are Zebu crossbred and Landim local breed. Zebu crossbred showed a significantly higher prevalence of BTB than the Landim local breed (49.6% vs 35.6%; OR 0.7, 95% CI: 45.4 – 53.9). Thirteen out of 67 positive blood samples were BOVIGAMTM positive. This study showed a high prevalence of BTB in the Govuro district. The findings reveal an urgent need for intervention with an implementation of effective, area-based, control measures in order to reduce prevalence and incidence of the disease and prevent its spread to the human population. Data also points that further studies on the isolation and molecular characterization of the predominant strains lineages that cause tuberculosis (TB) in cattle and humans should be conducted in order to assess the potential transmission of BTB from cattle to humans.
Em Moçambique, a tuberculose bovina (BTB) representa um sério problema para o desenvolvimento da pecuária, no entanto, os programas de vigilância e controle não são aplicados de forma consistente e sistemática. Esta doença tem repercussões económicas diretas na pecuária devido à baixa produtividade dos animais infetados, bem como o aumento da rejeição de carcaças ao nível dos matadouros. Devido às repercussões económicas diretas e consequências indiretas para a saúde humana, é de particular relevância conhecer a distribuição precisa da doença em todo o país de modo a definir uma estratégia de controlo eficaz e consequentemente reduzir as taxas de incidência e propagação da doença. Pesquisas não sistemáticas têm demonstrado uma grande variação da prevalência da doença em bovinos em diferentes regiões do país e até mesmo em rebanhos distintos de uma mesma região, porém a prevalência da doença nas espécies selvagens permanece desconhecida. Estudos anteriormente desenvolvidos em momentos diferentes no distrito de Govuro obtiveram taxas de prevalências dificilmente comparáveis; utilizando a tuberculinização simples na prega caudal (1.49%) e na tábua do pescoço (61.94%). Esta última representa uma das mais altas taxas de prevalência de BTB encontrada no país. No entanto, é de grande relevância considerar que, um resultado positivo obtido a partir do SITT pode estar relacionado com reatividade cruzada com micobactérias ambientais. Com o objetivo de determinar a prevalência da BTB em bovinos e identificar os fatores de risco associados à ocorrência da doença, desenvolveu-se um estudo transversal, no distrito de Govuro. Uma amostra representativa da população bovina pertencente a todas as áreas de produção do distrito (n=14) foi definida a partir do programa estatístico Epicalc 2000 (Brixton Books v.1 2), utilizando uma prevalência estimada de 10% e uma precisão de desvio padrão de 0.05 (5%). De modo a reduzir o efeito das incomparências (animais tuberculinizados que não comparecem no dia da leitura), foram testados 20% a mais do tamanho da amostra pré determinada. Um total de 1136 animais, pertencentes a 289 proprietários foi submetido a um teste de diagnóstico mais preciso, o teste tuberculínico comparativo (SCITT). Dados relativos a condição corporal, sexo, idade e raça foram registrados para obter uma melhor compreensão dos fatores de risco associados à doença. Os dados foram analisados utilizando um modelo de regressão logística com desfecho binário e a área de pecuária como efeito aleatório. A prevalência global estimada foi de 39.6% [95% com intervalo de confiança (CI): 36.8 – 42.5]. Com exceção da área de pecuária Luido (animais pertences a dois criadores privados) todas as restantes áreas estudadas apresentaram reatores positivos. Os resultados do SCITT mostraram que 137 (12%; 95% CI: 10.3 – 14.1) dos 1136 animais testados, reagiram positivamente ao PPD aviário. Dos 289 criadores incluídos no estudo, 192 (66.4%; 95% CI: 60.8 – 71.6) possuem animais positivos. A idade foi o principal fator de risco individual. Animais com mais de quatro anos mostraram-se mais propensos a ser reatores positivos (45.4% vs 21.9%; OR 2.9, 95% CI: 42,1 – 49,0). Animais do sexo feminino (37.2%; OR 1.1, 95% CI: 33.9 – 40.7) e com boa condição corporal (35.5%; OR 35, 95% CI: 32.0 – 39.1) foram associados a prevalências mais baixas, embora não tenham sido encontradas diferenças significativas. A maioria do gado incluído no presente estudo pertence à raça Zebu mestiços e raça local Landim. A raça mestiça Zebu apresentou uma prevalência de BTB significativamente maior em relação a raça Landim (49.6% vs 35.6%; OR 0,7, 95% CI: 45.4 – 53.9). Treze das 67 amostras de sangue positivas reagiram positivamente ao BOVIGAMTM. O presente estudo demonstrou uma alta prevalência de BTB no distrito de Govuro. Esses resultados revelam uma necessidade urgente de intervenção com implementação de medidas de controlo eficazes, baseados na área, de modo a reduzir a prevalência e incidência da doença e consequentemente evitar a sua propagação para o homem. Sugere-se que novos estudos sobre o isolamento e caracterização molecular das estirpes predominantes em bovinos e humanos sejam desenvolvidos de modo a avaliar a transmissão de BTB do gado bovino para o homem.
The laboratory work presented in this thesis was done in the Laboratory of Serology of Veterinary Faculty, Eduardo Mondlane University, Maputo, Mozambique and at the Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal. The financial support to perform this study was conceded by the Integrated Control of Neglected Zoonosis (ICONZ) – Africa Project and Fundação para a Ciência e a Tecnologia (FCT).
Prakhar, Praveen. "Wnt/β-Catenin-dependent Epigenetic Factors Shape Host Immune Responses During Mycobacterial Infection". Thesis, 2017. http://etd.iisc.ac.in/handle/2005/4226.
Повний текст джерелаAckah, Shiroma. "The association of demographics and occupational factors with latent tuberculosis infection in radiology staff at public sector hospitals in the eThekwini health district." Thesis, 2015. http://hdl.handle.net/10321/1422.
Повний текст джерелаIntroduction Tuberculosis remains a leading cause of death, second to the Human Immunodeficiency Virus. The risk of latent tuberculosis infection and active tuberculosis disease is a known occupational hazard. In South Africa, a high tuberculosis burden country, the potential of Mycobacterium tuberculosis transmission to health care workers is high. This includes diagnostic radiographers and other radiology staff working in radiology departments. Purpose of the Study This study aimed to investigate the association of demographic and occupational factors with latent tuberculosis infection in radiology staff in public sector hospitals of the eThekwini Health District. Methodology This cross-sectional study was conducted from 26 February 2013 to 07 June 2013. Quantitative methods were used to test for associations of demographic and occupational factors with latent tuberculosis infection in participants. A sample size of 181 participants for an estimated population of 340 radiology staff was recommended at the proposal stage. The study consisted of two phases; the questionnaire survey (phase one) and the administration of a two-step tuberculin skin test (phase two). Data was obtained with regard to demographics, occupational history, social behaviours, medical history; and family and home histories. Demographic and occupational associations with latent tuberculosis infection were made in relation to the size of the first tuberculin skin test induration. Frequency distributions were developed to describe data categories. Pearson’s and Spearman rho’ correlation coefficients were used to test for correlations between the independent variables. The chi-square test was used to determine associations between the categorical independent variables and the dependent variable. Bivariate analyses were performed using these tests. The multivariate analysis was performed using logistic and linear regression on the dependent variable. Results A total of 182 questionnaires were returned from approximately 280 radiology staff. At the outset, all doctors working in the radiology department had to be excluded due to numerous failed attempts to enlist their participation. Fifty-three (29.12 percent) participants were excluded from phase one of the study and a further thirteen participants were excluded from phase two. The total sample was 116 participants. Of the 116 participants, 86.2 percent tested positive for latent tuberculosis infection at the first step of the two-step testing method used. One (0.86 percent) participant went on to convert at the second step, testing positive at this level. Demographic associations with latent tuberculosis infection included age (older) as an associated factor. A significant demographic association with latent tuberculosis infection was the use of alcohol (p-value 0.033 on the multivariate analysis). Occupational associations with latent tuberculosis infection included longer durations of employment. The annual income (higher income earners) displayed significant associations with latent tuberculosis infection (p-value 0.048 on the multivariate analysis). It is necessary in this study to note that participants include support personnel (lower income earners) making up 37.8 percent of the study, diagnostic radiographers making up 48.3 percent; and radiography managers/assistant managers (highest income earners) making up 13.8 percent of the study. Conclusion and recommendations The risk of transmission of Mycobacterium Tuberculosis to health care workers is a known occupational hazard. This study has described the prevalence of latent tuberculosis infection in radiology staff, at district and regional hospitals within the eThekwini Health District. With 23.62 percent of all participants already having active TB disease and 86.2 percent of the tested group displaying positive results for latent tuberculosis infection, using the tuberculin skin tests, the need for tuberculosis screening is essential. The findings of this study will be used as a health improvement mechanism for stakeholders, having identified potential gaps in medical screening in healthcare in Kwa-Zulu Natal. This study makes recommendations for the early detection of active tuberculosis infection and the monitoring of health care workers that are latently infected, thus assisting in reducing the rate of conversion of latent tuberculosis infection to active tuberculosis disease in radiology staff. This reduces long-term exorbitant costs related to health care associated infections, such as tuberculosis. It also reduces rates of transmission and cross infection to both co-workers and already immunocompromised patients, helping to curb the overall epidemic in South Africa.