A major problem with breast cancer treatment is the prevalence of antiestrogen resistance, be it de novo or acquired after continued use. Many of the underlying mechanisms of antiestrogen resistance are not clear, although estrogen receptor-mediated actions have been identified as a pathway that is blocked by antiestrogens. Selective estrogen receptor modulators (SERMs), such as tamoxifen, are capable of producing reactive oxygen species (ROS) through metabolic activation, and these ROS, at high levels, can induce irreversible growth arrest that is similar to the growth arrest incurred by SERMs. This suggests that SERM-mediated growth arrest may also be through ROS accumulation. Breast cancer receiving long-term antiestrogen treatment appears to adapt to this increased, persistent level of ROS. This, in turn, leads to the disruption of reversible redox signaling that involves redox-sensitive phosphatases and protein kinases and transcription factors. This has downstream consequences for apoptosis, cell cycle progression, and cell metabolism. For this dissertation, we explored if altering the ROS formed by tamoxifen also alters sensitivity of the drug in resistant cells. We explored an association with a thioredoxin/Jab1/p27 pathway, and a possible role of dysregulation of thioredoxin-mediated redox regulation contributing to the development of antiestrogen resistance in breast cancer. We used standard laboratory techniques to perform proteomic assays that showed cell proliferation, protein concentrations, redox states, and protein-protein interactions. We found that increasing thioredoxin reductase levels, and thus increasing the amount of reduced thioredoxin, increased tamoxifen sensitivity in previously resistant cells, as well as altered estrogen and tamoxifen-induced ROS. We also found that decreasing levels of Jab1 protein also increased tamoxifen sensitivity, and that the downstream effects showed a decrease p27 phosphorylation in both cases. We conclude that the chronic use of tamoxifen can lead to an increase in ROS that alters cell signaling and causing cell growth in the presence of tamoxifen, and that this resistant cell growth can be reversed with an alteration to the thioredoxin/Jab1 pathway.

Arsenic exposure, through various routes, is associated with the development of cancer of the skin, lung, liver, kidney, and bladder. Treatment of cells in culture with trivalent arsenicals has been shown to increase reactive oxygen species (ROS). In particular, monomethylarsonous acid (MMAIII), a trivalent metabolite of arsenite, is highly cytotoxic and possibly carcinogenic. Three trivalent arsenicals; arsenite, arsenic trioxide (ATO), and MMAIII, are also known inhibitors of the selenoprotein thioredoxin reductase (TrxR). Selenium, an essential micronutrient in mammals, is needed in the form of selenocysteine for activity of this enzyme and other selenoproteins. TrxR is part of a key component of the cell's ability to defend against ROS. It has been speculated that TrxR is also involved directly in selenium metabolism, but this has yet to be demonstrated in vivo. The promoter region of the gene encoding the cytosolic TrxR (TrxR1) also contains an antioxidant responsive element (ARE). The ARE is activated by the transcription factor, Nrf2, which is governed by the Nrf2/Keap1 response, and can be triggered by certain oxidants. ATO and arsenite both inhibited incorporation of selenium into selenoproteins. Auranofin, a gold chemotherapeutic inhibitor of TrxR1, also inhibited selenoprotein synthesis. These results seem to support the hypothesis that TrxR1 is needed for selenoprotein synthesis. However, siRNA mediated reduction of TrxR1 did not block incorporation of selenium into selenoproteins. It is likely that ATO and auranofin are forming As-Se and Au-Se complexes, respectively. We also found that exposure of primary lung fibroblasts (WI-38) to MMAIII led to increased synthesis of TrxR1. This increase was dependent on the activation of transcription of the TrxR1 gene, specifically mediated through the ARE element. These results indicate exposure to MMAIII induces the Nrf2 response. The results obtained in these studies aid in both our understanding of the carcinogenic potential of arsenic as well as give new insight into the mechanism of action of emerging cancer drugs.

No description available.

Methanogens are a group of microorganisms that utilize simple compounds such as H₂ + CO₂, acetate and methanol for the production of methane, an end-product of their metabolism.  These obligate anaerobes belonging to the archaeal domain inhabit diverse anoxic environments such as rice paddy fields, human guts, rumen of ruminants, and hydrothermal vents.  In these habitats, methanogens are often exposed to O₂ and previous studies have shown that many methanogens are able to tolerate O2 exposure.  Hence, methanogens must have developed survival strategies to be able to live under oxidative stress conditions.  The anaerobic species that lived on Earth during the early oxygenation event were first to face oxidative stress.  Presumably some of the strategies employed by extant methanogens for combating oxidative stress were developed on early Earth.   Our laboratory is interested in studying the mechanism underlying the oxygen tolerance and oxidative stress responses in methanogenic archaea, which are obligate anaerobe.  Our research concerns two aspects of oxidative stress.  (i) Responses toward extracellular toxic species such as SO32-, that forms as a result of reactions of O₂ with reduced compounds in the environment.  These species are mostly seen in anaerobic environments upon O₂ exposure due to the abundance of reduced components therein.  (ii) Responses toward intracellular toxic species such as superoxide and hydrogen peroxide that are generated upon entry of O₂ and subsequent reaction of O₂ with reduced component inside the cell.  Aerobic microorganisms experience the second problem.  Since a large number of microorganisms of Earth are anaerobes and the oxidative defense mechanisms of anaerobes are relatively less studied, the research in our laboratory has focused on this area.  My thesis research covers two studies that fall in the above-mentioned two focus areas. In 2005-2007 our laboratory discovered that certain methanogens use an unusual sulfite reductase, named F420-dependent sulfite reductase (Fsr), for the detoxification of SO32- that is produced outside the cell from a reaction between oxygen and sulfide.  This reaction occurred during early oxygenation of Earth and continues to occur in deep-sea hydrothermal vents.  Fsr, a flavoprotein, carries out a 6-electron reduction of SO32- to S2-.  It is a chimeric protein where N- and C-terminal halves (Fsr-N and Fsr-C) are homologs of F420H2 dehydrogenase and dissimilatory sulfite reductase (Dsr), respectively.  We hypothesized that Fsr was developed in a methanogen from pre-existing parts.  To begin testing this hypothesis we have carried out bioinformatics analyses of methanogen genomes and found that both Fsr-N homologs and Fsr-C homologs are abundant in methanogens.  We called the Fsr-C homolog dissimilatory sulfite reductase-like protein (Dsr-LP).  Thus, Fsr was likely assembled from freestanding Fsr-N homologs and Dsr-like proteins (Dsr-LP) in methanogens.  During the course of this study, we also identified two new putative F420H2-dependent enzymes, namely F420H2-dependent glutamate synthase and assimilatory sulfite reductase. Another aspect of my research concerns the reactivation of proteins that are deactivated by the entry of oxygen inside the cell.  Here I focused specifically on the role of thioredoxin (Trx) in methanogens.  Trx, a small redox regulatory protein, is ubiquitous in all living cells.  In bacteria and eukarya, Trx regulates a wide variety of cellular processes including cell divison, biosynthesis and oxidative stress response.  Though some Trxs of methanogens have been structurally and biochemically characterized, their physiological roles in these organisms are unknown.  Our bioinformatics analysis suggested that Trx is ubiquitous in methanogens and the pattern of its distribution in various phylogenetic classes paralleled the respective evolutionary histories and metabolic versatilities.  Using a proteomics approach, we have identified 155 Trx targets in a hyperthermophilic phylogenetically deeply-rooted methanogen, Methanocaldococcus jannaschii.  Our analysis of two of these targets employing biochemical assays suggested that Trx is needed for reactivation of oxidatively deactivated enzymes in M. jannaschii.  To our knowledge, this is the first report on the role of Trx in an organism from the archaeal domain. During the course of our work on methanogen Trxs, we investigated the evolutionary histories of different Trx systems that are composed of Trxs and cognate Trx reductases.  In collaboration with other laboratories, we conducted bioinformatics analysis for the distribution of one of such systems, ferredoxin-dependent thioredoxin reductase (FTR), in all organisms.  We found that FTR was most likely originated in the phylogenetically deeply-rooted microaerophilic bacteria where it regulates CO₂ fixation via the reverse citric acid cycle. / Ph. D.

<p>Spermatogenesen är i många organismer en av de mest dramatiska förvandlingar som en cell kan genomgå – en vanlig, rund, diploid cell omvandlas till en nålformad, haploid cell med ett tätt packat cellmaskineri. I bananfluga, <i>Drosophila melanogaster</i>, innebär denna process flera karaktäristiska stadier. Ett av dessa är det primära spermatocyt-stadiet, som infaller innan cellen påbörjar meios-delning. Stadiet karaktäriseras av en uppluckrad kromatinstruktur i cellens kärna och ovanligt höga transkriptions- och translationshastigheter, för att producera allt det mRNA och de proteiner som behövs senare under spermatidomvandlingen. Två av de proteiner som uttrycks i höga nivåer i primära spermatocyter är ThioredoxinT (TrxT) och Painting of fourth (POF).</p><p>Thioredoxiner är små proteiner som har som funktion att reducera disulfidbryggor i andra proteiner, en mekanism som används i många olika fysiologiska sammanhang. I denna avhandling visar jag att <i>TrxT</i>-genen kodar för ett testikelspecifikt thioredoxin som binder specifikt till Y-kromosom-loopar i primära spermatocyter. <i>TrxT</i>-genen ligger precis bredvid <i>deadhead</i> (<i>dhd</i>), en gen som kodar för ett hon-specifikt thioredoxin som är lokaliserat till cellkärnorna i flugans äggstockar. Ett tredje thioredoxin i <i>Drosophila</i> är det allmänt uttryckta Thioredoxin-2 (Trx-2). Jag har upptäckt att flugor som saknar Trx-2 är livsdugliga, men att de lever kortare än vildtypsflugor, medan flugor med extra mycket Trx-2 har en ökad tålighet mot oxidativ stress. Slående nog är en total avsaknad av alla tre thioredoxiner inte förenat med letalitet, tvärtemot vad man skulle kunnat vänta sig. Alla tre thioredoxiner finns i de olika <i>Drosophilider</i> som undersökts och den ovanliga genorganisation som delas av <i>TrxT</i> och <i>dhd</i> är generellt konserverad.</p><p>Gen-namnet <i>Painting of fourth</i> härstammar från upptäckten att POF binder till (”målar”) <i>Drosophilas</i> kromosom 4. Jag visar i min avhandling att POFs bindning till den fjärde kromosomen är bevarad i olika <i>Drosophila</i>-arter och att POF kolokaliserar med både ett protein och en histon-modifiering, som är förknippade med doskompensation, i arter där POF också binder till hanens X-kromosom. POF uttrycks överallt i både honor och hanar, men i väldigt höga nivåer i hanens testiklar. Jag visar här att POF finns i cellkärnan hos primära spermatocyter, men också i kärnan på mognande spermatider, och att avsaknad av POF in hanens könsceller orsakar en global nedreglering av gener som ligger på kromosom 4. Kombinationen av mina POF- resultat tyder på att POF har en viktig funktion i det första kända fallet av genreglering av en hel autosomal kromosom.</p> / <p>The process of spermatogenesis is in many organisms one of the most dramatic cellular transformations - a normal round diploid cell is ultimately transformed into a needle shaped haploid cell with tightly packaged cell machinery. In <i>Drosophila melanogaster</i> this process involves several characteristic stages, one of these being the primary spermato-cyte stage, which is the stage prior to meiosis. This stage is characterized by a loose chromatin structure in the nucleus and exceptionally high rates of transcription and translation to produce essentially all the mRNAs and proteins that are needed later during spermatid formation. Two proteins that are expressed in high levels in primary spermatocytes are ThioredoxinT (TrxT) and Painting of fourth (POF).</p><p>Thioredoxins are small thiol proteins that reduce disulfides in other proteins, a mechanism that is utilized in many different contexts. In this thesis I show that the <i>TrxT</i> gene encodes a testis-specific thioredoxin that specifically associates to Y-chromosome loops in primary spermatocytes. <i>TrxT</i> is located right next to <i>deadhead</i> (<i>dhd</i>), a gene that encodes a female-specific thioredoxin that specifically locates to nuclei in the ovaries. A third thioredoxin in <i>Drosophila</i> is the ubiquitously expressed Thioredoxin-2 (Trx-2). I have found that flies lacking Trx-2 are viable but have shorter life spans than wild type flies, while over-expression of Trx-2 mediates an increased resistance to oxidative stress. Interestingly, a lack of all three thioredoxins does not result in lethality, contrary to what could be expected. All three thioredoxins are conserved among <i>Drosophilids</i> and the striking genomic organization of <i>TrxT</i> and <i>dhd</i> is generally conserved.</p><p>The gene name <i>Painting of fourth</i> originates from the finding that POF stains the 4th chromosome of <i>Drosophila</i> in a banded pattern on salivary gland chromosomes. I show in this thesis that POF binding to the equivalent of the 4th chromosome is conserved in genus <i>Drosophila</i> and that POF co-localizes with both a protein and a histone modification associated with dosage compensation in species where POF also binds the male X. POF is expressed ubiquitously in both males and females, but at very high levels in male testes. I show that POF is present in nuclei of primary spermatocytes, but also in nuclei of maturing spermatids and that a lack of POF in the male germline causes a global down-regulation of chromosome 4 genes. These results combined suggest a function of POF in the first known case of chromosome-wide gene regulation of an autosome.</p>

Spermatogenesen är i många organismer en av de mest dramatiska förvandlingar som en cell kan genomgå – en vanlig, rund, diploid cell omvandlas till en nålformad, haploid cell med ett tätt packat cellmaskineri. I bananfluga, Drosophila melanogaster, innebär denna process flera karaktäristiska stadier. Ett av dessa är det primära spermatocyt-stadiet, som infaller innan cellen påbörjar meios-delning. Stadiet karaktäriseras av en uppluckrad kromatinstruktur i cellens kärna och ovanligt höga transkriptions- och translationshastigheter, för att producera allt det mRNA och de proteiner som behövs senare under spermatidomvandlingen. Två av de proteiner som uttrycks i höga nivåer i primära spermatocyter är ThioredoxinT (TrxT) och Painting of fourth (POF). Thioredoxiner är små proteiner som har som funktion att reducera disulfidbryggor i andra proteiner, en mekanism som används i många olika fysiologiska sammanhang. I denna avhandling visar jag att TrxT-genen kodar för ett testikelspecifikt thioredoxin som binder specifikt till Y-kromosom-loopar i primära spermatocyter. TrxT-genen ligger precis bredvid deadhead (dhd), en gen som kodar för ett hon-specifikt thioredoxin som är lokaliserat till cellkärnorna i flugans äggstockar. Ett tredje thioredoxin i Drosophila är det allmänt uttryckta Thioredoxin-2 (Trx-2). Jag har upptäckt att flugor som saknar Trx-2 är livsdugliga, men att de lever kortare än vildtypsflugor, medan flugor med extra mycket Trx-2 har en ökad tålighet mot oxidativ stress. Slående nog är en total avsaknad av alla tre thioredoxiner inte förenat med letalitet, tvärtemot vad man skulle kunnat vänta sig. Alla tre thioredoxiner finns i de olika Drosophilider som undersökts och den ovanliga genorganisation som delas av TrxT och dhd är generellt konserverad. Gen-namnet Painting of fourth härstammar från upptäckten att POF binder till (”målar”) Drosophilas kromosom 4. Jag visar i min avhandling att POFs bindning till den fjärde kromosomen är bevarad i olika Drosophila-arter och att POF kolokaliserar med både ett protein och en histon-modifiering, som är förknippade med doskompensation, i arter där POF också binder till hanens X-kromosom. POF uttrycks överallt i både honor och hanar, men i väldigt höga nivåer i hanens testiklar. Jag visar här att POF finns i cellkärnan hos primära spermatocyter, men också i kärnan på mognande spermatider, och att avsaknad av POF in hanens könsceller orsakar en global nedreglering av gener som ligger på kromosom 4. Kombinationen av mina POF- resultat tyder på att POF har en viktig funktion i det första kända fallet av genreglering av en hel autosomal kromosom. / The process of spermatogenesis is in many organisms one of the most dramatic cellular transformations - a normal round diploid cell is ultimately transformed into a needle shaped haploid cell with tightly packaged cell machinery. In Drosophila melanogaster this process involves several characteristic stages, one of these being the primary spermato-cyte stage, which is the stage prior to meiosis. This stage is characterized by a loose chromatin structure in the nucleus and exceptionally high rates of transcription and translation to produce essentially all the mRNAs and proteins that are needed later during spermatid formation. Two proteins that are expressed in high levels in primary spermatocytes are ThioredoxinT (TrxT) and Painting of fourth (POF). Thioredoxins are small thiol proteins that reduce disulfides in other proteins, a mechanism that is utilized in many different contexts. In this thesis I show that the TrxT gene encodes a testis-specific thioredoxin that specifically associates to Y-chromosome loops in primary spermatocytes. TrxT is located right next to deadhead (dhd), a gene that encodes a female-specific thioredoxin that specifically locates to nuclei in the ovaries. A third thioredoxin in Drosophila is the ubiquitously expressed Thioredoxin-2 (Trx-2). I have found that flies lacking Trx-2 are viable but have shorter life spans than wild type flies, while over-expression of Trx-2 mediates an increased resistance to oxidative stress. Interestingly, a lack of all three thioredoxins does not result in lethality, contrary to what could be expected. All three thioredoxins are conserved among Drosophilids and the striking genomic organization of TrxT and dhd is generally conserved. The gene name Painting of fourth originates from the finding that POF stains the 4th chromosome of Drosophila in a banded pattern on salivary gland chromosomes. I show in this thesis that POF binding to the equivalent of the 4th chromosome is conserved in genus Drosophila and that POF co-localizes with both a protein and a histone modification associated with dosage compensation in species where POF also binds the male X. POF is expressed ubiquitously in both males and females, but at very high levels in male testes. I show that POF is present in nuclei of primary spermatocytes, but also in nuclei of maturing spermatids and that a lack of POF in the male germline causes a global down-regulation of chromosome 4 genes. These results combined suggest a function of POF in the first known case of chromosome-wide gene regulation of an autosome.

The study aimed to investigate the following: 1. Investigate a putative glutathione peroxidase gene (Glyma17g34110) within Glycine max by an in silico analysis and spatial expression. 2. Determine the effects of exogenously applied nitric oxide on the expression of Glyma17g34110. 3. Investigate the antioxidant mechanism with attention to Glyma17g34110,reactive oxygen species and cell death in the response to salt stress. 4. Establish whether Glyma17g34110 is a glutathione peroxidase or thioredoxindependent peroxidase gene. / Magister Scientiae - MSc

The production of reactive oxygen species (ROS) is prominent in all aerobic metabolisms including plants. For this reason, the redox homeostasis of the production and scavenging of these intermediates is imperative for growth, development and survival during unfavourable conditions. In this study, a putative glutathione peroxidase gene (Glyma17g34110) from Glycine max (soybean) was identified and analyzed. The successful characterisation of Glyma17g34110 provided evidence of it being a glutathione peroxidase using glutathione as its preferred electron donor and substrate. Furthermore, it is known that antioxidant enzymes such as GPX exist in various tissues, performing a diverse set of functions. By a bioinformatic analysis of Glyma17g34110 and its promoter region, it was indicated that Glyma17g34110 could be a putative chloroplast protein that could play an important role in photosynthesis.One of the major factors affecting plant growth and development worldwide is abiotic stresses such as salinity. In the presence of salinity the production of harmful ROS is increased, resulting in detrimental reactions with important biological features (DNA, protein and lipid membranes), leading to cell death. The analysis of Glyma17g34110 under salt stress revealed that it is a salt sensitive gene and thus, the down-regulation of Glyma17g34110 could be due to the lack of known defence and response cis-acting elements present in the promoter region. Furthermore, it was proven in previous studies that the application of exogenous nitric oxide (NO) increases the activity of antioxidant enzymes. In this thesis it was observed that the presence of exogenously applied NO increased the expression of Glyma17g34110 tremendously in all soybean tissues (leaves, roots and nodules) investigated.Studies have found numerous cis-acting elements to be NO responsive, however, none of these elements were found in the promoter region upstream of glyma17g34110. This suggests that novel cis-acting elements could be present in the promoter region of Glyma17g34110.Thus, increasing the expression of Glyma17g34110 during salinity in the presence of NO, as well as the identification of these novel cis-acting elements, could lead to the enhancement of the defence mechanisms against ROS, which could lead to increasing plant tolerance to stress. / >Magister Scientiae - MSc

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Submitted by LIEGE ABDALLAH KAWAI null (liegekawai@gmail.com) on 2017-12-13T13:56:50Z No. of bitstreams: 1 liege kawai - tese final.pdf: 5173025 bytes, checksum: 74d38826e72cc45ba04c0050ac6a409b (MD5) / Approved for entry into archive by Elza Mitiko Sato null (elzasato@ibilce.unesp.br) on 2017-12-13T14:57:31Z (GMT) No. of bitstreams: 1 kawai_la_dr_sjrp.pdf: 5173025 bytes, checksum: 74d38826e72cc45ba04c0050ac6a409b (MD5) / Made available in DSpace on 2017-12-13T14:57:31Z (GMT). No. of bitstreams: 1 kawai_la_dr_sjrp.pdf: 5173025 bytes, checksum: 74d38826e72cc45ba04c0050ac6a409b (MD5) Previous issue date: 2017-11-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Corynebacterium pseudotuberculosis (C. pseudotuberculosis), é uma bactéria gram positiva anaeróbia facultativa, pleomórfica, que não esporula, não forma cápsula, e que apresenta 2 biotipos ou biovares, sendo o biovar equi capaz de infectar preferencialmente equinos, enquanto o biótipo denominado ovis acomete pequenos ruminantes. Esta bactéria faz parte do grupo CMNR (Corynebacterium, Mycobacterium, Nocardia e Rhodococcus), que demonstra grande importância veterinária e médica, uma vez que estes micro-organismos comumente infectam animais, podendo infectar o homem, causando perdas econômicas pela ineficácia ou alto custo de terapias existentes. Um exemplo seria a linfadenite caseosa (LC) causada por C. pseudotuberculosis, que afeta particularmente a pecuária de caprinos e ovinos, com a condenação da carcaça e redução da produção de lã e de carne. A transmissão da doença e contágio dos animais é direta, muitas vezes através da alimentação e ingestão de água em local contaminado por animais doentes. Essa doença possui incidência na pecuária mundial, principalmente de caprinos e ovinos, havendo registros de ocorrência no Brasil, Europa, Oriente Médio, Austrália, Nova Zelândia, África do Sul, Canadá e Estados Unidos e mesmo com todos os avanços tecnológicos, ainda não há métodos de prevenção totalmente eficazes, como vacinas e medicamentos, tampouco para o tratamento de animais infectados, que geralmente são de custo elevado, por longos períodos e sem a garantia de cura ou de isenção de reincidência da LC. Deste modo, técnicas mais rápidas e fáceis para detecção e diagnóstico da doença, bem como para seu tratamento, se tornam imprescindíveis, evitando não só a disseminação da doença, mas também suas consequentes perdas econômicas. Atualmente, devido ao uso indiscriminado de antibióticos para o tratamento de infecções de origem bacteriana, bem como à constante exposição destes micro-organismos a essas drogas em ambientes hospitalares, observa-se o desenvolvimento de micro-organismos resistentes às terapias disponíveis, sendo um desafio mundial a descoberta e elaboração de tratamentos eficazes para a prevenção, controle e eliminação destes patógenos, como alternativa aos já existentes. Visando terapias alternativas e direcionadas para infecção por C. pseudotuberculosis, as proteínas tioredoxina, tioredoxina redutase e diphtheria toxin repressor foram estudadas no presente trabalho, a fim de melhor compreender este micro-organismo. / Corynebacterium pseudotuberculosis (C. pseudotuberculosis), is a gram-positive, facultative anaerobe, pleomorphic, non-sporulating bacterium with two biotopes or biovars, being the biovar equi capable of infecting horses, whereas the biotype called ovis infects small ruminants. It is part of the CMNR group (Corynebacterium, Mycobacterium, Nocardia and Rhodococcus), which demonstrates great veterinary and medical importance, since these common microorganisms infect animals and can infect humans, causing economic losses due to the inefficiency or high cost of existing therapies. An example is a caseous lymphadenitis (LC) caused by C. pseudotuberculosis, which particularly affects the goats and sheep livestock, with carcass condemnation and reduction of wool and meat production. The transmission of disease and the contagion of animals is direct, often through feeding and drinking water in places contaminated by sick animals. This disease has an incidence in the world livestock, mainly of goats and sheep, with occurrence records in Brazil, Europe, the Middle East, Australia, New Zealand, South Africa, Canada and the United States and even with all technological advances, still there are no totally effective prevention methods, such as vaccines and medications, nor for the treatment of infected animals, which are usually of a high cost, for long periods and without guarantee of cure or exemption from recurrence of LC. In this way, faster and easier techniques for the detection of the diagnosis of this disease as well as for its treatment become essential, avoiding not only a spread of the disease, but also its consequent economic losses. Currently, the use of indiscriminate antibiotics for the treatment of infections of bacterial origin, as well as the constant exposure of these microorganisms to these drugs in hospital environments, shows the development of microorganisms resistant to the available therapies, being one world-wide challenge the elaboration of effective treatments for the prevention, control and elimination of these pathogens, as an alternative to the existing ones. Aiming alternative therapies for infection by C. pseudotuberculosis, proteins such as thioredoxin, thioredoxin reductase, diphtheria toxin repressor, were studied in the present work, for a better comprehension of this microorganism.