Submitted by Cássio da Cruz Nogueira (cassionogueirakk@gmail.com) on 2017-01-05T12:31:55Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_InvestigacaoPolimorfimosGenes.PDF: 1141933 bytes, checksum: 471a75c00025493bea9afec0bcc8cf90 (MD5) / Approved for entry into archive by Edisangela Bastos (edisangela@ufpa.br) on 2017-01-09T17:53:54Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_InvestigacaoPolimorfimosGenes.PDF: 1141933 bytes, checksum: 471a75c00025493bea9afec0bcc8cf90 (MD5) / Made available in DSpace on 2017-01-09T17:53:54Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_InvestigacaoPolimorfimosGenes.PDF: 1141933 bytes, checksum: 471a75c00025493bea9afec0bcc8cf90 (MD5) Previous issue date: 2015-11-06 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Tuberculose pulmonar é uma doença infectocontagiosa de transmissão por via aérea, que segundo a Organização Mundial de Saúde (OMS), infecta cerca dois bilhões de pessoas ao redor do mundo. É a principal causa de morte por doença infecciosa em adultos nos países em desenvolvimento, representando um grave problema de saúde pública, devido principalmente, a não aderência ao tratamento, ao diagnóstico tardio e subdiagnóstico e ao não controle de contatos, o que faz com que a população continue susceptível à infecção. No presente estudo se objetivou investigar associações de três polimorfismos genéticos nos genes IFNɣ e INFGR1, responsáveis pela suscetibilidade à tuberculose em pacientes acometidos pela doença; avaliar se ocorrem diferenças nas frequências alélicas e genotípicas dos polimorfismos nos genes IFNɣ871A>T, INFGR1611(C>T) e INFGR1 -56(A>G) entre indivíduos com tuberculose e indivíduos sem tuberculose da população de Belém. O controle de efeito de subestruturação foi realizado pelo emprego de um painel de 48 Marcadores Informativos de Ancestralidade Genética, tanto na amostra de pacientes como na amostra controle. Para realização deste estudo nos utilizamos amostras de sangue periférico de 148 pacientes diagnosticados com tuberculose,e 125 indivíduos sem tuberculose (controles) residentes no Estado do Pará, Brasil, atendidos no Hospital Universitário João de Barros Barreto (HUJBB) durante o período de 2006 a 2012.De cada indivíduo foram obtidos 5mL de sangue venoso colhido de veia periférica.A extração de DNA foi realizada segundo método descrito por Sambrook et al., (1989).A genotipagem dos polimorfismos para os genes IFNɣ(rs1130562) e INFGR1 (rs1327474, rs2234711) foi realizada por técnica de PCR em tempo real (Rtq-PCR) utilizando-se o sistema TaqMan.As análises estatísticas foram realizadas nos softwares SPSS 17.0, usando o teste de Mann-Whitney, considerando como significantes valores de p<0,05. Os resultados obtidos não demonstraram significância dos polimorfismos investigados em relação a suscetibilidade para tuberculose. / Pulmonary tuberculosis is an infectious disease transmission by air, which according to the World Health Organization (WHO), infects about two billion people around the world. It is the leading cause of death from infectious disease in adults in developing countries, representing a serious public health problem, mainly due to non-adherence to treatment, late diagnosis and underdiagnosis and no control contacts, which makes our population susceptible to infection. The present study aimed to investigate associations three genetic polymorphisms in IFNɣ and INFGR1 genes responsible for susceptibility to tuberculosis in patients affected by the disease; evaluate if there are differences in allelic and genotypic frequencies of polymorphisms in genes IFNɣ 871A> T, INFGR1 611 (C> T) and INFGR1 -56 (A> G) among individuals with TB and those without TB population of Bethlehem. The control substructures effect was carried out by the use ofa 48 markers Informational Genetic Ancestry panel in both patient sample and the control sample. For this study we used peripheral blood samples from 148 patients diagnosed with tuberculosis, and 125 individuals without tuberculosis (controls) resident in the State of Pará, Brazil, attended at University Hospital João de Barros Barreto (HUJBB) during the period from 2006 to 2012. each specimen was obtained 5 ml of venous blood collected from a peripheral vein. DNA extraction was performed according to the method described by Sambrook et al., (1989). Genotyping for polymorphisms IFNɣ gene (rs1130562) and INFGR1 (rs1327474, rs2234711) was performed by PCR in real time (RTQ-PCR) using the TaqMan system. Statistical analyzes were performed in SPSS 17.0 software, using the Mann- Whitney test, with significance set at p <0.05. The results did not show significance of the polymorphisms investigated in relation to susceptibility to tuberculosis.

abstract: One of the two objectives of this dissertation is an investigation into the possible correlation between rainfall events and increased levels of E. coli and Mycobacterium using an existing data set. The literature states that levels of microbial concentrations do increase after rainfall events, but there are no studies to indicate this correlation applies in any Arizona water systems. The data analyzed for the bacterial concentrations project suggested the possibility of a correlation along one river but it is not conclusive to state that any correlation exists between rainfall events and the microbial concentration for many other sites included in the analysis. This is most likely due to the highly engineered water delivery systems that are not directly impacted. The secondary objective was to determine if there are environmental variables collected from an ongoing project which would be a good candidate for making predictions about any of the project data parameters. Of the 79 possible opportunities for the model to accurately predict the dependent variable, it showed strong statistical favorability as well as experimentally favorable results towards Dissolved Organic Carbon as the best dependent variable from the data set, resulting in an accuracy of 41%. This is relevant since Dissolved Organic Carbon is one of the most important water quality parameters of concern for drinking water treatment plants where disinfection by-products are a limiting factor. The need for further analysis and additional data collection is an obvious result from both studies. The use of hydrograph data instead of rainfall would be a logical new direction for the heavily engineered water delivery systems. / Dissertation/Thesis / Masters Thesis Civil, Environmental and Sustainable Engineering 2018

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death from an infectious disease worldwide. Over the course of its life cycle in vivo, Mtb is exposed to a plethora of environmental stress conditions. Temporal regulation of genes involved in sensing and responding to such conditions is therefore crucial for Mtb to establish an infection. The Rv2745c (clgR) gene encodes a Clp protease gene regulator that is induced in response to a variety of stress conditions and potentially plays a role in Mtb pathogenesis. Our isogenic Mtb:ΔRv2745c mutant is significantly more sensitive to in vitro redox stress generated by diamide, relative to wild-type Mtb, implicating a role for ClgR in the management of intraphagosomal redox stress. Our data indicates that ClgR plays a role in multiple regulatory networks in response to different stress conditions. Thus, redox stress leads to dysregulation of the σH/σE regulon in Mtb:ΔRv2745c. Induction of clgR in Mtb and Mtb:ΔRv2745c (comp) did not lead to Clp protease induction, indicating that clgR has additional functions. Disruption of genes involved in sulfate assimilation also occurred in the knock out, implicating clgR as a possible regulator of downstream signaling cascades that facilitate Mtb survival. On the other hand, the expression of clgR during hypoxia is known to result in Clp protease induction. As such, the isogenic mutant has a significantly different growth profile upon hypoxia and reaeration. Transcriptomics reveal disruption of the dosR regulon, σH/σE regulon, and mycolic acid synthesis genes. Clearly, the Mtb Rv2745c-encoded ClgR performs different functions during stress response and is important for the pathogenicity of Mtb in vivo. Our in vivo findings in a low dose aerosolized model reveal deficiencies of the isogenic mutant when establishing an infection, leading to skewed immune responses throughout the course of infection. Thus, clgR plays a critical role in both establishing an infection that influence the immunogenic outcome. Additional studies investigating the role of clgR in a nonhuman primate model will further elucidate the contributions of clgR to the pathogenesis of Mtb in an animal model that is more representative of human TB disease. / acase@tulane.edu

In spite of vaccine and treatment strategies, Mycobacterium tuberculosis kills more than 3 people per minute. The emergence of drug-resistant strains makes treating the disease complicated and expensive for government health departments, and unpleasant and laborious for patients. The current vaccine, parenterally administered BCG, is only 50% effective. Oral vaccination has the advantage of targeting the mucosal immune system, which acts at the direct site of initial exposure to the infecting airborne pathogen. In addition, oral vaccines are cheaper and safer to administer than parenteral vaccines. This dissertation provides a conceptual framework for the prevention of the disease by means of oral vaccination and outlines methods that were developed for the production of concentrated purified somatic and extracellular antigens. Immune responses to somatic antigens were also examined in conjunction with established and novel adjuvants. The role of Propionibacterium jensenii 702 as a suitable mucosal adjuvant was supported by the results obtained. / Masters Thesis

Johne�s disease in ruminants is caused by the pathogenic bacterium Mycobacterium avium subspecies paratuberculosis. An experimental infection model in sheep was developed as a prelude to the testing of new vaccines and the development of improved diagnostic assays for Johne�s disease. The final challenge model developed used four doses of 10⁹ viable organisms given at two to three day intervals. Gross and microscopic lesions were found in a high proportion of sheep (80%) at ten months post challenge. There was considerable variation in immune responses from animals challenged with different strains of M. paratuberculosis. Sheep challenged with a low passage laboratory culture of strain (W) M. paratuberculosis, produced strong lymphocyte transformation responses and Interferon gamma (IFN-γ) production at two months post challenge. Subsequent necropsy and culture from intestinal tissues showed only a low level of infection (25%). In comparison a primary tissue isolate of M. paratuberculosis (JD3) resulted in higher (60-90%) infection rates in orally challenged animals. The immune profile from these animals showed very little reactivity for the first three months post challenge, after which IFN-γ production could be detected. Antibody production and lymphocyte transformation response could not be measured until at least seven months post challenge. Sheep challenged with the primary tissue isolate instilled directly into the tonsil resulted in equivalent levels of Johne�s disease to those obtained with oral challenge. However, intratonsillar challenge resulted in higher levels of immune reactivity than oral challenge. The proprietary Johne�s vaccines; NeoparsecTM and GudairTM and an Aqueous vaccine were tested in sheep. The immunological reactions of the sheep to these vaccines showed some variations between the two separate studies, with the NeoparasecTM and GudairTM vaccines evoking high levels of CMI and humoral reactivity within two months of vaccination. Detailed immunological examination of gut associated lymphoid tissues were carried out on subgroups of animals that were either vaccinated or non-vaccinated and went on to develop disease or were immune to experimental challenge. The results showed that the diseased animals examined had multibacillary lesions and strong CMI and humoral responses. There were decreased proportions of CD4⁺, CD8⁺ and CD25⁺ T cells in peripheral blood and gut associated lymphatics of diseased animals compared with the immune or unchallenged subgroups. Profiles from the immune subgroups showed a stronger lymphocyte transformation response than case matched diseased animals. Tissues from immune animals showed increased proportions of B cells above those seen in diseased or unchallenged animals. This study has resulted in the development of a robust experimental sheep model in which Johne�s disease occurs in a high proportion of challenged animals. Critical time points for the establishment of infection or disease have been determined. It can be used in the future to evaluate protective efficacy of vaccines or to critically chart immunological profiles that are associated with infection, disease or protective immunity. Considerable research is needed to develop improved diagnostic tests to identify patterns of immunity during the early stages of infection or while the animal has subclinical disease.

Le 2-éthylhexyl nitrate (2-EHN) est incorporé en quantité significative au gazole afin d'augmenter son indice de cétane. Ce composé est produit à raison de 100 000 tonnes par an, principalement en France. Les risques liés à son utilisation sont cependant mal connus car en cas de contamination de l'environnement, on ne sait pas s'il est biodégradable. Cette étude avait pour but (i) d'évaluer la capacité de biodégradation du 2-EHN par des bactéries sélectionnées, (ii) d'élucider la voie de dégradation, et (iii) d'identifier les enzymes impliquées. Les tests de biodégradation prenant en compte le caractère toxique et hydrophobe du substrat on été mis au point dans un premier temps. A l'aide de ces tests qui reposent sur la mise en oeuvre de cultures biphasiques, nous avons montré que plusieurs souches de Mycobacterium austroafricanum étaient capables de dégrader le 2-EHN. La souche la plus performante (IFP 2173), résistant à des concentrations de 2-EHN de 6 g.L-1, a été choisie pour étudier la voie de dégradation. Sur la base de bilans carbone et d'analyse du milieu de culture par chromatographie gazeuse (CG), j'ai découvert que la dégradation du 2-EHN était incomplète et donnait lieu à l'accumulation d'un métabolite. Ce métabolite a été identifié comme étant la β-méthyl-γ-butyrolactone par des analyses de CG-MS et LC-MS/MS. La structure de cette lactone indiquait que le 2-EHN était dégradé selon une voie enzymatique impliquant l'hydroxylation du groupement méthyle de la chaîne carbonée principale, son oxydation en aldéhyde et acide, et enfin un cycle de β-oxydation. <br>Dans un deuxième temps, les enzymes impliquées dans la voie de dégradation du 2-EHN ont été recherchées par une approche protéomique. Des analyses par électrophorèse bidimensionnelle ont mis en évidence qu'en présence de 2-EHN, la souche IFP 2173 déclenche la synthèse d'une panoplie d'enzymes spécialisées dans le métabolisme des acides gras, comme les enzymes de la β-oxydation, des alcool et aldéhyde déshydrogénases. Une analyse exhaustive du protéome de la souche IFP 2173 a permis d'identifier par LC-MS/MS plus de 200 protéines induites sur 2-EHN, notamment un cytochrome P450 de type alcane monooxygénase (CYP153). En outre, j'ai également identifié et cloné les gènes codant deux alcanes hydroxylases transmembranaires de types AlkB, qui n'ont pas été détectées par l'approche protéomique. Ainsi, la souche IFP 2173 possède trois alcane hydroxylases susceptibles de catalyser l'attaque initiale du 2-EHN. Pour déterminer laquelle de ces trois monooxygénases était responsable de cette réaction, leur gène respectif a été cloné dans des plasmides conçus pour l'expression soit chez E. coli, soit chez M. smegmatis mc². Nos résultats préliminaires montrent que dans certains cas les protéines recombinantes sont bien synthétisées. Ces constructions seront employées pour étudier l'activité des trois hydroxylases de IFP 2173 vis-à-vis des alcanes et du 2-EHN en particulier.

This study evaluated the potential of the aerobic Mycobacterium strain JS6O to grow on a variety of organic acid substrates, and the possible effects an organic acid would have on the degradation rate of vinyl chloride (VC). A series of batch growth tests were designed to determine the time it took to consume the substrate and the overall increase in biomass. Strain JS6O was found capable of growth on acetate, propionate, and butyrate, but could not grow on formate or lactate. Acetate was chosen for further study because strain JS6O consumed acetate the most rapidly of all the organic acids tested, and acetate is a common product of fermentation reactions in the subsurface. Strain JS6O was confirmed to grow on both ethylene and vinyl chloride as the sole carbon and energy source. Comparatively, strain JS6O's rate of growth on VC is much slower than that of ethylene. With acetate as an augmenting growth substrate, ethylene and VC utilization rates increased by 30% and 48%, respectively. Since acetate and VC are often found together in contaminated chlorinated ethene plumes, this makes a strong case for natural attenuation of VC by strain JS6O. A series of kinetic tests were implemented to determine the K[subscript s] and k[subscript max] of strain JS6O for ethylene, VC, and c-DCE. The K[subscript s] and k[subscript max] for ethylene determined through NLSR methods was similar to the values published in Coleman et al. (2002), supporting the maintenance of a pure culture throughout the experimental work. When strain JS6O was exposed to the isomers of DCE (trans-1,2-dichloroethylene (t-DCE), cis-1,2-dichloroethylene (c-DCE), and 1,1-dichloroethylene (1,1-DCE)) the cells were unable to grow on these compounds. However, when growing on acetate, strain JS6O cometabolized c-DCE and t-DCE, but not 1,1-DCE, with c-DCE transformed more rapidly than t-DCE. Transformation of c-DCE was also observed with growth on VC and ethylene. The presence of c-DCE was shown to partially inhibit VC degradation, but had no effect on ethylene degradation. The cometabolism results with acetate further indicate that strain JS6O is a good candidate for natural attenuation of multiple chlorinated ethenes in the subsurface. / Graduation date: 2006

In paleopathology, the assessment of disease occurs through macroscopic observation, which is dependent on the preservation of the sample and the experience of the observer. Many disease events do not leave any visible signatures and therefore go undetected. The relatively new field of paleomicrobiology incorporates molecular techniques where microbial DNA, if present, is amplified from an archaeological sample. The identification of genetic material from micro-organisms, including bacteria and viruses, can confirm a diagnosis that was originally based on visible osteological or mummified tissue changes. Even more promising is the capability of molecular technology to detect microbial DNA evidence of disease processes that were not visibly evident.<p> Based on phylogenetic analyses of modern isolates, scientists have concluded that micro-organisms such as <i>Mycobacterium tuberculosis</i> and <i>Helicobacter pylori</i> have been associated with humans for thousands of years. <i>M. tuberculosis</i> is the causative agent of the disease tuberculosis, and <i>H. pylori</i> is known for its role in gastritis and peptic ulcers. Both are pathogenic bacteria that still impact the health of modern populations. Through the analysis of microbial DNA from these two bacteria in skeletal and mummified tissue, data can be accumulated regarding the spatial and temporal impact of these infections. Interestingly, due to the lengthy association between these bacteria and humans, phylogenetic studies on modern strains have shown that strain characterizations of both <i>M. tuberculosis</i> and <i>H. pylori</i> bacteria reveal connections with past human migrations.<p> In 1999, human remains were discovered eroding out of a glacier in northern British Columbia, Canada on the traditional territory of the Champagne and Aishihik First Nations. The Aboriginal elders named the site Kwäday Dän Tsìnchi, which means long ago person found. Radiocarbon testing of bone collagen and artifacts from the site suggested a time-frame of approximately AD 1670 to 1850, which is either pre-European contact or early post-contact for that area. I analyzed the tissues of the ancient individual specifically for genetic evidence of <i>M. tuberculosis</i> and <i>H. pylori</i> to identify partial health status and determine if a connection could be made to strains associated with European populations to clarify whether the site was pre or post-European contact.<p> Through polymerase chain reaction (PCR) testing of the individuals tissues with primers specific for the IS<i>6100</i> insertion sequence, <i>TbD1</i>, and <i>Rv3479</i>, <i>katG</i> and <i>gyrB</i> genes, I identified evidence of a possible latent tuberculosis infection. Genetic characterization of the <i>katG</i> gene associated with the ancient <i>M. tuberculosis</i> strain revealed a potential connection with European strains. Amplification and sequencing of the <i>gyrB</i> gene fragment indicated the presence of two alleles that may have been the result of a selective pressure.<p> PCR testing of the individuals stomach tissue with specific primers for regions with the <i>vacA</i> gene resulted in a positive identification of <i>H. pylori</i> DNA. Genetic characterization of this virulence-associated gene indicated that the strain contained a <i>vacA</i> signal (s) region s2 allele. This allele is more commonly identified in Western strains that do not cause disease, which suggests that the individual had no gastric symptoms and that European strains were present in northwestern Canada at that time. The vacA middle (m) region contained a hybrid m2a/m1d sequence. Modern hybrids are rare but they have been identified in Asian strains. Studies have shown that the m2a allele is more common in Western strains. A phylogenetic analysis identified that the m1d region clusters with previously published novel strains associated with Aboriginal individuals that are closely related to Asian strains. This indicates a past connection between the ancient individual and his ancestors who arrived in the New World from Asia thousands of years ago.

In paleopathology, the assessment of disease occurs through macroscopic observation, which is dependent on the preservation of the sample and the experience of the observer. Many disease events do not leave any visible signatures and therefore go undetected. The relatively new field of paleomicrobiology incorporates molecular techniques where microbial DNA, if present, is amplified from an archaeological sample. The identification of genetic material from micro-organisms, including bacteria and viruses, can confirm a diagnosis that was originally based on visible osteological or mummified tissue changes. Even more promising is the capability of molecular technology to detect microbial DNA evidence of disease processes that were not visibly evident.<p> Based on phylogenetic analyses of modern isolates, scientists have concluded that micro-organisms such as <i>Mycobacterium tuberculosis</i> and <i>Helicobacter pylori</i> have been associated with humans for thousands of years. <i>M. tuberculosis</i> is the causative agent of the disease tuberculosis, and <i>H. pylori</i> is known for its role in gastritis and peptic ulcers. Both are pathogenic bacteria that still impact the health of modern populations. Through the analysis of microbial DNA from these two bacteria in skeletal and mummified tissue, data can be accumulated regarding the spatial and temporal impact of these infections. Interestingly, due to the lengthy association between these bacteria and humans, phylogenetic studies on modern strains have shown that strain characterizations of both <i>M. tuberculosis</i> and <i>H. pylori</i> bacteria reveal connections with past human migrations.<p> In 1999, human remains were discovered eroding out of a glacier in northern British Columbia, Canada on the traditional territory of the Champagne and Aishihik First Nations. The Aboriginal elders named the site Kwäday Dän Tsìnchi, which means long ago person found. Radiocarbon testing of bone collagen and artifacts from the site suggested a time-frame of approximately AD 1670 to 1850, which is either pre-European contact or early post-contact for that area. I analyzed the tissues of the ancient individual specifically for genetic evidence of <i>M. tuberculosis</i> and <i>H. pylori</i> to identify partial health status and determine if a connection could be made to strains associated with European populations to clarify whether the site was pre or post-European contact.<p> Through polymerase chain reaction (PCR) testing of the individuals tissues with primers specific for the IS<i>6100</i> insertion sequence, <i>TbD1</i>, and <i>Rv3479</i>, <i>katG</i> and <i>gyrB</i> genes, I identified evidence of a possible latent tuberculosis infection. Genetic characterization of the <i>katG</i> gene associated with the ancient <i>M. tuberculosis</i> strain revealed a potential connection with European strains. Amplification and sequencing of the <i>gyrB</i> gene fragment indicated the presence of two alleles that may have been the result of a selective pressure.<p> PCR testing of the individuals stomach tissue with specific primers for regions with the <i>vacA</i> gene resulted in a positive identification of <i>H. pylori</i> DNA. Genetic characterization of this virulence-associated gene indicated that the strain contained a <i>vacA</i> signal (s) region s2 allele. This allele is more commonly identified in Western strains that do not cause disease, which suggests that the individual had no gastric symptoms and that European strains were present in northwestern Canada at that time. The vacA middle (m) region contained a hybrid m2a/m1d sequence. Modern hybrids are rare but they have been identified in Asian strains. Studies have shown that the m2a allele is more common in Western strains. A phylogenetic analysis identified that the m1d region clusters with previously published novel strains associated with Aboriginal individuals that are closely related to Asian strains. This indicates a past connection between the ancient individual and his ancestors who arrived in the New World from Asia thousands of years ago.

Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. The high incidence is still found in Taiwan. There is strong evidence that host genes influence individual susceptibility to tuberculosis. Young children, like immunocompromised patients, once infected are at increased risk for TB disease and progression to extrapulmonary disease. Thus far, to identify the genes responsible for the variation in the human susceptibility/resistance to TB has remained elusive. Mannose-binding lectin (MBL) activates the complement system in an antibody-independent manner, enhances complement-mediated phagocytosis, and plays an important role in innate immunity in the regulation of inflammatory cytokine release by monocytes. It is one of the molecules that have been suggested to have a link to human susceptibility or protection against infection. According to some studies (mostly conducted in adult populations) , low levels of MBL associated with variant alleles at the promoter and exon 1 regions of MBL protect against tuberculosis. Other investigators instead claim that protection against the disease is associated with high levels of MBL. In this study we aimed to investigate the relationships between the susceptibility to TB and MBL gene polymorphisms in children with cervical mycobacterial lymphadenitis infected by M. tuberculosis.139 case patients with cervical mycobacterial lymphadenitis and 102 unrelated healthy control subjects were tested by real-time PCR for polymorphisms at the promoter and the exon 1 regions of the MBL gene. Diagnosis of mycobacterial lymphadenitis infected by M. tuberculosis, based on findings of pathological examination of the lymph nodes, was confirmed by acid-fast stain and TB PCR.The frequency of A allele was significantly higher in TB+ patients compared with TB- controls (82.7% vs 72.6%; odds ratio 1.813; p=0.007). The frequency of high-producer MBL2 genotypes (A/A) was higher in TB+ patients than in TB- subjects (70.5% vs 45.1%, odds ratio 2.91, p<0.001), while patients carried the B alleles (A/B and B/B) that have decreased levels of MBL was inversely associated with mycobacterial infectivity (29.5% vs 54.9%; odds ratio 2.910; p<0.001). The frequencies of MBL promoter -550 genotypes also revealed a significant difference between TB+ and TB- groups (p = 0.046), but in contrast, with significantly higher frequency of L/L genotype (of low MBL level) in TB+ patients (34.5% vs 21.6%; odds ratio 1.918; p=0.029). The frequencies of MBL promoter -221 genotypes (X and Y) was similar in TB+ and TB- groups.This study supports the conclusion that MBL can protect or predispose the host to tuberculosis, depending on the host¡¦s haplotype pair.