A tuberculose, doença infecto-contagiosa causada pelo Mycobacterium tuberculosis (Mtb), constitui, em escala mundial, um sério problema de saúde pública, com altos índices de morbidade e mortalidade. Alguns grupos são mais suscetíveis à doença, como é o caso das populações indígenas brasileiras. Estudos prévios indicam um risco dez vezes maior de contrair a tuberculose, e morrer devido a ela, nessas populações do que na população brasileira como um todo. Exemplos disso são as altas incidências de tuberculose em indivíduos da etnia Xavante. Evidências sugerem um forte componente genético na suscetibilidade à tuberculose e aos fenótipos relacionados à doença. Um desses fenótipos é a anergia ao PPD, isto é, a ausência de reatividade ao teste que utiliza derivados de proteína purificada da bactéria para verificar resposta imune celular e diagnosticar infecção pelo Mtb. Vários são os genes associados à suscetibilidade à tuberculose ou à infecção pelo bacilo em diferentes populações. Com o objetivo de investigar essa suscetibilidade genética em ameríndios brasileiros, neste estudo foram analisados 19 polimorfismos em 15 genes envolvidos com a resposta imune já identificados com resistência/suscetibilidade à tuberculose (SLC11A1, VDR, SP110, P2X7, PTPN22, IL1B, IL12RB1, IFNGR1, TNFR1, IFNG, IL2, IL10, IL6, IL4 e IL4R). A amostra foi composta por 492 indivíduos de uma população da etnia Xavante, da aldeia Etéñitépa, localizada no Estado de Mato Grosso, região central do Brasil. Os seguintes resultados foram obtidos: a) redução ou ausência de variabilidade em seis variantes (SP110 éxon 11 C>T e íntron 6 C>T, PTPN22 1858 C>T, IL12RB1 641 A>G e 1094 T>C e IL6 -174 G>C); b) associação entre os polimorfismos IFNG +874 A>T e IL4 -590 T>C e reatividade ao PPD (P=0,018 e 0,009, respectivamente). Após ajustes na regressão de Poisson com variância robusta, os genótipos IFNG +874 T/A e IL4 -590 C/C foram duas vezes mais prevalentes do que seus genótipos complementares (1,9; CI: 1,1-3,1 e 2,0; CI: 1,2-3,3, respectivamente); c) o polimorfismo IL10 -1082 A>G foi associado com anergia ao PPD (P<0,001); o risco de anergia foi de 1,5 (CI: 1,2-1,7) em indivíduos homozigotos para o alelo G, comparados com portadores do alelo A; d) em relação à reatividade ao PPD, nenhum dos outros polimorfismos mostrou alguma associação; e) não foram observadas associações significativas entre os genes estudados e tuberculose. Os resultados obtidos sugerem que o componente genético tem uma grande influência nos mecanismos imunes relacionados à anergia ao PPD e, conseqüentemente, à infecção pelo Mtb nos Xavante.Apesar da ausência de associações em relação à tuberculose, há uma complexidade dos fatores genéticos nas doenças infecciosas e o envolvimento de muitos genes na etiologia da doença. Portanto, a replicação deste estudo em outros grupos indígenas e a pesquisa de outros genes, que poderiam estar envolvidos com a suscetibilidade à tuberculose e aos fenótipos a ela relacionados, são essenciais para se ter um melhor entendimento do sistema imune humano e seus complexos mecanismos de resposta, podendo fornecer, futuramente, novos alvos para tratamentos preventivos e profiláticos diferenciados para grupos étnicos específicos. / Tuberculosis is an infectious disease which is caused by Mycobacterium tuberculosis (Mtb). It constitutes a serious problem in public health, causing high standards of morbidity and mortality all over the world. Some groups are more susceptible to the disease such as, for example, the Brazilian indigenous populations. According to previous studies, the risk of getting this disease and consequently die from it is ten times higher for indigenous populations than for the Brazilian population in general. As an example of this phenomenon, there is the Xavante group. These individuals suffer from a high incidence of tuberculosis among them. Evidences suggest a strong genetic component related to this susceptibility to tuberculosis, and to the phenotypes related to the disease as well. One of these phenotypes is anergy to PPD, i.e., the absence of reactivity to the test in which derivatives of the purified protein from the bacteria are employed, in order to check an immune cellular response and to diagnose infection by Mtb. There are many genes associated with the susceptibility to tuberculosis or to the infection through the bacillus in different populations. The aim of this study was to investigate TB genetic susceptibility in Brazilian Amerindians, considering 19 polymorphisms in 15 genes involved in the immune response, previously identified with resistance/susceptibility to tuberculosis (SLC11A1, VDR, SP110, P2X7, PTPN22, IL1B, IL12RB1, IFNGR1, TNFR1, IFNG, IL2, IL10, IL6, IL4, and IL4R). The sample was composed by 492 individuals from a Xavante population, at the Etéñitépa village, Mato Grosso State, Central Brazil. The following results were obtained: a) reduction or absence of variability in six variants (SP110 exon 11 C>T and intron 6 C>T, PTPN22 1858 C>T, IL12RB1 641 A>G and 1094 T>C and IL6 -174 G>C); b) association between the polymorphisms IFNG +874 A>T and IL4 -590 T>C and reactivity to PPD (P=0.018 and 0.009, respectively); after adjustments by Poisson regression with robust variance the IFNG +874 T/A and IL4 -590 C/C genotypes were two times more prevalent than their complementary genotypes (1.9; CI: 1.1-3.1 e 2.0; CI: 1.2- 3.3, respectively); c) IL10 -1082 A>G polymorphism was associated with anergy to PDD (P<0.001); the risk of anergy was 1.5 (CI: 1.2-1.7) in G/G homozygous individuals when compared with carriers for the A allele; d) in relation to reactivity to PPD, no associations were observed for the other polymorphisms; e) no associations were observed between the genes studied and tuberculosis. The results suggest that the genetic component has a important influence in immune mechanisms related to PPD anergy, and therefore to the infection by Mtb in the Xavante group. In spite of the absence of association related to tuberculosis, there is also a great complexity of genetic factors in infectious diseases, and the involvement of many genes in the disease etiology. Consequently, the replication of this study in other indigenous groups and also the investigation of other genes that could be involved with susceptibility to tuberculosis and to phenotypes related to it as well are essential. In this way, we would have a better understanding of the human immune system and its complex mechanisms of response. This research could provide, in the future, new targets for preventive and prophylactic treatments that would be different, according to specific ethnic groups.

Made available in DSpace on 2014-06-12T15:52:51Z (GMT). No. of bitstreams: 2 arquivo4560_1.pdf: 2458717 bytes, checksum: 858cc2a51da4970f6d0139a6ebb0f940 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2007 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / O presente trabalho avalia a caracterização físico-química e a atividade antimicobacteriana in vitro do ácido úsnico (AU) encapsulado em nanocápsulas (NC-AU) de copolímero de ácido D,L-(láctico-glicólico) (PLGA) (50:50). O espectro de infravermelho da NC-AU mostrou uma banda de absorção em 1750 cm-1 atribuído aos grupos ésteres do PLGA. As bandas de absorção nas faixas de 1635 e 1190 cm-1 foram referentes ao grupo aromático da cetona e ao grupo fenil do ácido úsnico, respectivamente. A análise de calorimetria diferencial de varredura (DSC) da NC-AU revelou a presença de um pico endotérmico em 45,5 °C com variação da entalpia de 23,8 J/g. Enquanto que o AU apresentou um único pico endotérmico em 201,7 ºC referente ao seu ponto de fusão, com variação da entalpia de 85,2 J/g. A encapsulação do ácido úsnico ocorreu sem interação molecular com o polímero. A análise termogravimétrica da NC-AU e da nanocápsula vazia (NC) mostrou duas fases de degradação, enquanto que o AU apresentou uma única fase de decomposição. Nenhuma perda de peso da NC-AU e da NC foi observada até 50 °C, sugerindo que as amostras foram estáveis até essa temperatura. A susceptibilidade do M. tuberculosis ao AU e NC-AU foi de 7,98 e 3,83 &#956;g/mL, respectivamente. A análise da atividade intracelular revelou um aumento de 30% na atividade antimicobacteriana do AU quando encapsulado nas nanocápsulas de PLGA. Dessa maneira, conclui-se que a encapsulação em nanocápsulas de PLGA potencializa a atividade antimicobacteriana in vitro do AU

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No. of bitstreams: 1 Dissertação - Cláudia Maria de Melo Silva.pdf: 2215806 bytes, checksum: c9afeecd5c357af061e1b38a8a31df56 (MD5) Previous issue date: 2014-04-28 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / Tuberculosis (TB) is a chronic infection caused by Mycobacterium tuberculosis complex and remains a major worldwide public health problem, leading to almost 1.45 million deaths annually. The state of Amazonas has a high rate incidence of TB, about 68.3/100,000 inhabitants in 2012. Only 5 to 10% of infected individuals develop active TB. It has been suggested that host factors determine the immune response to pathogen. Thus, many immunogenetic researches have demonstrated TB associated genes, but in the north region, research in this field is still rare. This fact motivated the investigation of polymorphisms for IFNG, IL12B, CD80 and CD86 genes, which codify proteins for cellular immune response. Furthermore, IFN- concentration and its relation with genotypes found have been verified. A total of 177 patients and 224 controls (159 contacts and 65 non-contacts) were included in this study and DNA sequencing was performed for genes IFNG (SNP +874A/T and microsatellite +875), IL12B (SNPs +1030C/T, +1188A/C and +1254T/G), CD80 (SNPs -454 C/A, -387 T/C, -232 G/A, -79 C/G, -7T/C, +5C/A and an indel polymorphism -557_-561insCATGA) and CD86 (SNPs +1057G/A and +1079G/A). The IFN-y concentration was determined by enzyme-linked immunoassay. At IFNG, the presence of the allele +874A and the allele with 15 CA repeats were associated with susceptibility to pulmonary TB, while the allele +874T and the allele with 12 CA repeats were associated with protection from pulmonary TB. In addition, an association between genotype CC (SNP +1188A/C at IL12B) and increased risk of pulmonary TB was found. Furthermore, a significant difference between IFN- concentration and genotypes of SNP +1188A/C at IL12B and microsatellite at IFNG was observed, with decrease of IFN-at genotype CC and 15 CA repeats respectively. These outcomes lead to a better understanding of the immune response regulation for TB and help to determine the genetic profile of the Amazon population. Future researches are still needed for a better understanding of the role of other genes involved in the immune response to M. tuberculosis and their influence at the production of citokines like IFN-. / A Tuberculose (TB) é uma infecção crônica causada pelo complexo Mycobacterium tuberculosis sendo um importante problema de saúde pública mundial, levando a aproximadamente 1,45 milhões de mortes a cada ano. O estado do Amazonas possui uma alta incidência desta doença, atingindo 68,3 casos por 100 mil habitantes em 2012. Dos indivíduos infectados pelo bacilo, cerca de 5 a 10% desenvolvem a Tuberculose ativa, sugerindo que há fatores associados ao hospedeiro que determinam o destino da resposta imune ao patógeno. Neste contexto, diversos estudos em imunogenética têm demonstrado genes associados à TB, mas na região norte ainda são raras as pesquisas nesta área, fato que motivou a investigação da frequência dos polimorfismos nos genes IFNG, IL12B, CD80 e CD86, que codificam para proteínas fundamentais na resposta imune celular. Além disso, foi verificado se a concentração de IFN- está relacionada com o genótipo encontrado. Foram incluídas amostras de 177 pacientes e 224 controles (159 contatos e 65 não contatos) e realizado sequenciamento de DNA para os genes IFNG (SNP +874A/T e microssatélite +875), IL12B (SNPs +1030C/T, +1188A/C e +1254T/G), CD80 (SNPs -454 C/A, -387 T/C, -232 G/A, -79 C/G, -7T/C e +5C/A e um polimorfismo indel -557_-561insCATGA) e CD86 (SNPs +1057G/A e +1079G/A). A determinação das concentrações de IFN-foi realizada através de ensaio imunoenzimático. Foi verificada uma associação do gene IFNG, entre a presença do alelo +874A e 15 repetições CA, como fator de risco para TB pulmonar assim como a presença do alelo +874T e 12 repetições CA como fatores de proteção contra TB pulmonar. Também foi encontrada uma associação do genótipo CC, do SNP +1188A/C no gene IL12B, como fator de risco ao desenvolvimento da TB pulmonar. Houve diferença significativa na concentração de IFN-entre os genótipos do SNP +1188A/C no gene IL12B e o microssatélite no gene IFNG, com menor produção no genótipo CC e 15 repetições CA respectivamente. Estes resultados contribuem para o melhor entendimento da regulação na resposta imune à TB e auxilia na determinação do perfil genético da população da região Amazônica. Estudos futuros são necessários para uma melhor compreensão do papel de outros genes envolvidos na resposta imunológica a M. tuberculosis e influência nos níveis de produção de citocinas como IFN-.

A Pirazinamida (Z), droga de primeira linha usada no tratamento da tuberculose, necessita ser hidrolisada pela enzima bacteriana pirazinamidase (PZase) para que o seu metabólito ativo, o ácido pirazinóico (POA), possa agir. O principal mecanismo molecular de resistência a esta droga envolve mutações no gene pncA, que codifica a PZase. Com base nestas informações e tendo em vista a ausência de estudos acerca de resistência à Z em isolados clínicos de M. tuberculosis em nosso país, o presente trabalho propôs caracterizar as mutações envolvendo o gene pncA, bem como relacioná-las com os resultados do teste de atividade da enzima PZase e da concentração inibitória mínima (CIM) de Z. A caracterização molecular dos isolados foi realizada por \"Spoligotyping\", sendo que, todos os isolados testados foram confirmados como pertencentes à espécie M. tuberculosis. A CIM foi realizada por três metodologias: técnica em microplaca utilizando o Alamar Azul como revelador (MABA), método de microdiluição em caldo (BMM), e método das proporções em Lowenstein-Jensen. Os resultados obtidos dão conta de uma boa associação entre as metodologias, e a determinação da CIM pelo método MABA mostrou-se uma nova e segura opção a ser utilizada para Z. A maioria dos isolados clínicos de M. tuberculosis resistentes à Z (88%), apresentaram também atividade de PZase negativa, bem como mutações no gene pncA. Algumas exceções foram encontradas, já que 12% dos isolados clínicos resistentes não apresentaram mutações no gene pncA e tiveram atividade da PZase positiva, sugerindo a existência de outro mecanismo envolvido com resistência à Z. Das 22 mutações encontradas no gene pncA, 9 estão sendo descritas apenas neste estudo. Registrou-se também a presença de 5 isolados clínicos apresentando fenótipo de monorresistência à Z. / Pyrazinamide (Z), a first-line antituberculous drug, is a prodrug that must be activated by bacterial pyrazinamidase (PZase) to the active form pyrazinoic acid, which kills M. tuberculosis. Many studies have shown that mutation in the gene encoding PZase (pncA) is the major mechanism of Z-resistance in M. tuberculosis. Based on this information and taking into consideration the absence of studies concerning Z-resistance in Brazilian M. tuberculosis strains, this study was aimed at characterizing pncA mutations and investigating its correlation with Z-resistance and PZase activity. The molecular characterization carried out by Spoligotyping revealed that all tested strains belong to M. tuberculosis species. The minimal inhibitory concentration (MIC) of Z was determined by three methods: microplate Alamar Blue assay (MABA), broth microdilution method (BMM) and method of proportions on Lowenstein-Jensen medium. The results showed a good association between the 3 methods, and MABA for MIC determination signalized a new and safe option to be used for Z. Most of Z-resistant strains (88%) presented pncA mutations as well as loss of PZase activity. Some exceptions were found since 12% of Z-resistant strains presented neither pncA mutations nor loss of PZase activity, what suggests the existence of another Z-resistance mechanism. Nine of 22 mutations found in pncA gene were described only in this study. During the course of this investigation were identified 5 Z-monoresistant M. tuberculosis strains.

No description available.

In this thesis, we explore the benefits of microencapsulating isoniazid and pyrazinamide within sporopollenin exine capsules derived from Lycopodium clavatum. Sporopollenin is a natural biopolymer, which is extracted from the outer shell of pollen grains. These hollow microcapsules can encapsulate and release drug actives in a controlled manner and possess many other advantages such as homogeneity in morphology and size, resilience to both strong acids and bases, they have antioxidant properties as well as UV protection to protect the material inside the microcapsule. Compared to artificial microcapsules, sporopollenin’s muco-adhesion to intestinal tissues contributes greatly to the extended contact of the sporopollenin with the intestines leading to an increased efficiency of delivery of drugs. The hollow microcapsules can be easily filled with a solution of the active or active in a liquid form by simply mixing both together. The drug actives are released in the human body depending on pH factors. Active release can otherwise have controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell so that high drug concentrations are delivered to the site of infection. Encapsulation of the drug active will possibly improve therapeutic abilities of the drugs; simplify the treatment of TB-HIV coinfections by eliminating troublesome drug-drug interactions and drastically reduce or eliminates side effects. The SECs were loaded using a passive filling method. The drug active (0.1 g) was dissolved in a solvent and mixed with the SECs (0.1 g) for 10 minutes. After mixing for 10 minutes, the solvent was removed by a rotary evaporator and dried to a constant mass. The surface of the sporopollenin exines were analysed on a FTIR to observe if there are any drug deposits on the surface of the SECs. The loading efficiency and drug release percentage was determined by using calibrations curves and analysed on a UV-vis spectrophotometer. Further work has been proposed in which to characterize the SECs further and producing coated tablets from loaded SECs.

M.Sc. (Biochemistry) / Tuberculosis (TB) is an infectious disease that worldwide, is more prevalent in Africans compared to Caucasians. TB also affects males to a greater extent than females. Genetic associations between VDR sequence variants and TB is often inconsistent across different populations. Epigenetic and environmental factors, as well as ethnicity may confound associations found between VDR and TB...

The World Health Organization (WHO) estimated that eight million new cases of tuberculosis (TB) occur every year and that one-third of the world’s population is infected with Mycobacterium tuberculosis (M. tuberculosis). With the increase in HIV/AIDS in the 1980’s, an increase in transmission of TB led to an increase in TB incidence. A study showed that South African adults (ages 15 to 49) will suffer 278 154 deaths between 2008 and 2017 if current control measures are continued. A M. tuberculosis strain that is resistant to isoniazid (INH) and rifampicin (RIF) used in the treatment of TB is known as a multi-drug resistant (MDR-TB) strain. In extensively drugresistant tuberculosis (XDR-TB) the M. tuberculosis strains are not only resistant to INH, RIF and any one of the fluoroquinolones but to at least one of the three injectable second-line drugs such as amikacin or kanamycin. Unfortunately, many people with XDR-TB will die because it is virtually impossible to formulate an effective treatment before the resistance pattern of the M. tuberculosis strain has been identified. Bacteriological culture is considered the diagnostic gold standard and can identify mycobacteria in over 80% of TB cases, with a specificity of over 98%. However, culturing the mycobacteria takes 4 to 6 weeks and makes diagnosis and treatment a prolonged process. In this study 60 patients suspected of TB disease, from the Anti-retroviral (ARV) clinic at the Tshwane District Hospital (TDH) were collected from October 2008 to April 2009. This study evaluated the use of the QuantiFERON-TB GOLD ELISA assay in a high burden setting. Tshwane District Hospital, South Africa. The sensitivity and specificity of the QFT assay in the clinic were 30% (9/30) and 63% (19/30) respectively when compared to the gold standard culture results. Analysis suggested that the sensitivity of the QuantiFERON assay is determined by a limiting patient CD4 value of between 150 and 200. Real-time PCR assays were used for rapid identification of Mycobacterium spp and to determine the presence of isoniazid and rifampicin resistant genes of M. tuberculosis strains. The real-time PCR assay identified 28% (17/60) M. tuberculosis, 2% (1/60) M. kansasii and 70% (42/60) of the isolates Mycobacterium spp negative. No M. avium were detected. The 17 M. tuberculosis positive specimens were further analysed for the presence of INH and RIF resistance genes. All 17 specimens had either no mutation or one or more mutations at the specific gene targets (rpo1, rpo2, katG and inhA). This study showed several possibilities for the use of both an immunological assay as well as molecular methods for the diagnosis of TB. This study suggested that in terms of routine diagnosis of TB in high HIV prevalence settings the QFT test should be used with caution. Realtime PCR for both detection and identification showed useful results and can be used together with culture results to improve turnaround times for TB diagnosis. Copyright / Dissertation (MSc)--University of Pretoria, 2010. / Medical Microbiology / unrestricted

Tuberculosis (TB) is the leading cause of death among HIV infected people. Mycobacterium tuberculosis (M. tuberculosis), the causative agent of TB, features a distinctive lipid-rich cell wall with mycolic acids (MA) the major component in the outer layer. Mycolic acids are á-alkyl â-hydroxy long chain fatty acids, which exist in a number of chemical subclasses depending on the presence of functional oxygenated and non-oxygenated groups in the meromycolate chain. In numerous studies the different MA subclasses have been shown to play different roles in antibody recognition, virulence and the ability to attract cholesterol. It was previously suggested that the oxygenated MA might be important for these properties. Except for the mycolic acid motif, little is known about the stereochemistry of the other chiral centres. The importance of the different functional groups, their position and stereochemistry, for immunological properties, are not yet clarified. This study set out to resolve the structureactivity relationships of mycolic acids from M. tuberculosis in terms of their antigenicity and the ability to attract cholesterol. To determine fine specificity of interaction of MA with antibodies, the subclasses of MA from M. tuberculosis were separated and the antigenicity of two was determined. TB+ and TB- patient sera recognised natural MA, alpha-MA and methoxy-MA. It was confirmed that the carboxylic acid group played a fundamental role in its recognition. Interestingly, cord factor (trehalose-6,6’-dimycolate) was recognised specifically by TB+ sera. This implies multiple epitopes in the MA structure, some of which are very specific for TB patients. A stereocontrolled diastereomer of cis-cyclopropane methoxy-MA was synthesized and along with other synthetic methoxy-, keto- and hydroxy-MAs, were tested for antibody recognition. One diastereomer, SS-SR-methoxy-MA, was recognised stronger by TB+ serum than the other, it also is the one that closest approximates the signal strength of antibody binding to natural MA by TB+ patient sera. While the others are not specifically recognised, this SS-SR-methoxy-MA may well represent one of the antigenically active components that occurs in natural MA and that elicits specific antibodies in TB patients. This thesis reports a stereocontrolled chemical synthesis of biologically active mycolic acids and shows that a single component of the mycolic acid mixture can be sufficient to elicit an immunological response. / Thesis (PHD)--University of Pretoria, 2008. / Biochemistry / unrestricted

Les nucléomodulines sont des protéines produites par des bactéries parasites intracellulaires et qui sont importées dans le noyau des cellules infectées pour y moduler l'expression génique et contribuer ainsi à la virulence de la bactéries. L'identification de nucléomodulines chez plusieurs espèces de bactéries pathogènes a fait émerger ce concept comme une stratégie supplémentaire utilisée par les parasites intracellulaires pour contourner les moyens de défense de l'hôte. Le but de cette thèse était d'identifier et d'analyser d'éventuelles nucléomodulines produites par l'agent étiologique de la tuberculose, la bactérie Mycobacterium tuberculosis (Mtb). Nous avons tout d'abord analysé le génome de Mtb, à la recherche de gènes dont les produits portent des séquences analogues aux séquences de localisation nucléaire des eucaryotes (NLS). Nous avons pu identifier deux gènes de Mtb, Rv0229c et Rv3876, qui codent des protéines sécrétées dans le milieu de culture et qui se localisent dans le noyau lorsqu'elles sont exprimées dans des cellules épithéliales ou dans des macrophages murins ou humains. Les NLS de ces deux protéines ont été identifiées et leur modification abolit la localisation nucléaire dans les cellules eucaryotes. Le gène Rv0229c est trouvé spécifiquement dans le génome des espèces pathogènes du complexe Mtb. Ce gène semble avoir été acquis récemment par l'ancêtre de Mtb, via un transfert génétique horizontal. Rv3876 est plus généralement distribué chez les mycobactéries, et appartient à une région génomique codant un système de sécrétion type VII, ESX1, essentiel pour la virulence de Mtb. Les travaux en cours visent à analyser la dynamique de ces deux protéines au cours de l'infection de macrophages ou de modèles animaux, et leur rôle en tant que modulateurs de l'expression génique des cellules infectées et dans la virulence de Mtb. / The nuclear targeting of bacterial proteins that modify host cell gene expression, the so-called nucleomodulins, has emerged as a novel mechanism contributing to virulence of several intracellular pathogens. The goal of this study was to identify nucleomodulins produced by Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and to investigate their role upon infection of the host. We first performed a screening of Mtb genome in search of genes encoding proteins with putative eukaryotic-like nuclear localization signals (NLS). We identified two genes of Mtb, Rv0229c and Rv3876, encoding proteins that are secreted in the medium by Mtb and are localized into the nucleus when expressed in epithelial cells or in human or murine macrophages. The NLSs of these two proteins were identified and found to be essential for their nuclear localization. The gene Rv0229c, a putative RNase, is present only in pathogen species of the Mtb complex and seems to have been recently acquired by horizontal gene transfer (HGT). Rv3876 appears more widely distributed in mycobacteria, and belongs to a chromosomal region encoding proteins of the type VII secretion system ESX1, essential for virulence. Ongoing studies are currently investigating the dynamics of these proteins upon infection of host cells, and their putative role in the modulation of host cell gene expression and Mtb virulence.