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INTRODUCTION: Chronic venous insufficiency (CVI) is an anomaly of the normal functioning of the venous system caused by valvular incompetence with or without the obstruction of venous flow. This condition can affect either or both of the superficial and the deep venous systems. Venous dysfunction can even result in congenital or acquired disorders, and its complications include venous leg ulcers (VLUs). The objective of this systematic review is to determine the effectiveness of Unna boot in the treatment of wound healing of VLU by assessing the quality of the available evidence. METHODS AND ANALYSIS: A literature search in PubMed, CINAHL, Scopus, Web of Science, Cochrane Library, BVS/BIREME, Embase, ProQuest, BDTD, Thesis and Dissertation Catalog, Sao Paulo Research Foundation/Thesis and dissertation, OPEN THESIS, A service of the US National Institute of Health, Center for Reviews and Dissemination-University of New York and SciElo published in the last 10 years, the period from January 1999 to March 2019. The review will include primary studies (original), and Controlled Trials or Observational studies (cross-sectional, case-control or longitudinal studies) with VLU. The exclusion will include leg ulceration due to different causes, such as pressure, arterial, diabetic or mixed-aetiology leg ulcers. Data synthesis will be performed using a narrative summary and quantitative analysis. ETHICS AND DISSEMINATION: This systematic review does not require approval by the ethics committee, as individual patient data will not be collected. Dissemination of findings will be through publications in peer-reviewed journals and/or via conference presentations. PROSPERO REGISTRATION NUMBER: CRD42019127947.
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Curativos Oclusivos/normas , Úlcera Varicosa/terapia , Humanos , Extremidade Inferior/irrigação sanguínea , Úlcera Varicosa/etiologia , Insuficiência Venosa/complicações , Cicatrização , Revisões Sistemáticas como AssuntoRESUMO
OBJECTIVE: To describe the clinical characteristics of Latin American patients with metastatic renal cell carcinoma (mRCC) who experienced a progression-free survival (PFS) for at least 15 months following treatment with sunitinib. PATIENTS AND METHODS: In this retrospective analysis, mRCC patients in two institutions in Latin America received sunitinib at a starting dose of either 50 mg/day for 4 weeks followed by 2 weeks off treatment (Schedule 4/2) in repeated 6-week cycles or sunitinib 37.5 mg on a continuous daily dosing schedule. Clinical characteristics, tolerability, and PFS data were collected. RESULTS: Twenty-nine patients with long-term clinical benefit from sunitinib were identified between September 2005 and August 2009. Median PFS was 23 months (range: 15-54 months). Two of the 29 patients with prolonged PFS achieved a complete response and additional eleven had a partial response. Most patients were aged <60 years, had good performance status, favorable or intermediate Memorial Sloan Kettering Cancer Center prognostic risk, and disease limited to one or two sites. Dose reduction was necessary in all patients who started sunitinib at 50 mg/day administered on Schedule 4/2. Adverse events leading to dose reduction included grade 3 hand-foot syndrome, mucositis, fatigue, and hypertension. At the time of data cutoff, four patients were still receiving sunitinib treatment. CONCLUSION: Extended PFS can be achieved in Latin American patients with mRCC treated with sunitinib. Although the small sample size and retrospective nature of this evaluation preclude the identification of pretreatment predictive factors contributing to this benefit, the current analysis warrants further investigation using a larger data set in this population.
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Clinical conditions associated with obesity can be improved by daily intake of conjugated linoleic acid (CLA) or extra virgin olive oil (EVOO). Here we investigated whether dietary supplementation with CLA and EVOO, either alone or in combination, changes body metabolism associated with mitochondrial energetics. Male C57Bl/6 mice were divided into one of four groups: CLA (1:1 cis-9, trans-11:trans-10, cis-12; 18:2 isomers), EVOO, CLA plus EVOO or control (linoleic acid). Each mouse received 3 g/kg body weight of the stated oil by gavage on alternating days for 60 days. Dietary supplementation with CLA, alone or in combination with EVOO: (a) reduced the white adipose tissue gain; (b) increased body VO2 consumption, VCO2 production and energy expenditure; (c) elevated uncoupling protein (UCP)-2 expression and UCP activity in isolated liver mitochondria. This organelle, when energized with NAD(+)-linked substrates, produced high amounts of H2O2 without inducing oxidative damage. Dietary supplementation with EVOO alone did not change any metabolic parameter, but supplementation with CLA itself promoted insulin resistance and elevated weight, lipid content and acetyl-CoA carboxylase-1 expression in liver. Interestingly, the in vivo antioxidant therapy with N-acetylcysteine abolished the CLA-induced rise of body metabolism and liver UCP expression and activity, while the in vitro antioxidant treatment with catalase mitigated the CLA-dependent UCP-2 expression in hepatocytes; these findings suggest the participation of an oxidative-dependent pathway. Therefore, this study clarifies the mechanisms by which CLA induces liver UCP expression and activity, and demonstrates for the first time the beneficial effects of combined CLA and EVOO supplementation.
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Metabolismo Energético/efeitos dos fármacos , Hipertrofia/prevenção & controle , Resistência à Insulina , Ácidos Linoleicos Conjugados/farmacologia , Fígado/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Azeite de Oliva/farmacologia , Animais , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.
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Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Resistência à Doença/imunologia , Esquistossomose/imunologia , Vacinas/imunologia , Adolescente , Adulto , Anticorpos Anti-Helmínticos/imunologia , Brasil/epidemiologia , Doença Crônica , Análise por Conglomerados , Doenças Endêmicas , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/imunologia , Análise Serial de Proteínas , Esquistossomose/sangue , Esquistossomose/epidemiologia , Adulto JovemRESUMO
Daily intake of conjugated linoleic acid (CLA) has been shown to reduce body fat accumulation and to increase body metabolism; this latter effect has been often associated with the up-regulation of uncoupling proteins (UCPs). Here we addressed the effects of a CLA-supplemented murine diet (~2 % CLA mixture, cis-9, trans-10 and trans-10, cis-12 isomers; 45 % of each isomer on alternating days) on mitochondrial energetics, UCP2 expression/activity in the liver and other associated morphological and functional parameters, in C57BL/6 mice. Diet supplementation with CLA reduced both lipid accumulation in adipose tissues and triacylglycerol plasma levels, but did not augment hepatic lipid storage. Livers of mice fed a diet supplemented with CLA showed high UCP2 mRNA levels and the isolated hepatic mitochondria showed indications of UCP activity: in the presence of guanosine diphosphate, the higher stimulation of respiration promoted by linoleic acid in mitochondria from the CLA mice was almost completely reduced to the level of the stimulation from the control mice. Despite the increased generation of reactive oxygen species through oxi-reduction reactions involving NAD(+)/NADH in the Krebs cycle, no oxidative stress was observed in the liver. In addition, in the absence of free fatty acids, basal respiration rates and the phosphorylating efficiency of mitochondria were preserved. These results indicate a beneficial and secure dose of CLA for diet supplementation in mice, which induces UCP2 overexpression and UCP activity in mitochondria while preserving the lipid composition and redox state of the liver.
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Suplementos Nutricionais , Endopeptidases/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Ácidos Linoleicos Conjugados/farmacologia , Fígado/metabolismo , Mitocôndrias Hepáticas/metabolismo , Animais , Masculino , Camundongos , NAD/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteases Específicas de UbiquitinaRESUMO
The expectations that shade-tolerant forest species show 1) a population structure composed by a high amount of small individuals, and 2) biomass allocation for diameter higher than for height growth, were tested for Rudgea parquioides, a typical shrub in Southern Brazil. We described the size structure (height and stem diameter) and allometrical relations of a R. parquioides population by counting and measuring all the individuals in a 725m² area in the municipality of Curitiba (25"25'S; 49"19'W). A total of 916 individuals (12,634 ind.ha-1) were recorded in the area. The firstexpectation was supported, since distribution by height and diameter classes showed a predominance of small individuals (skewness coefficients > 1). On the other hand, the regression between height and stem base diameter showed slope β < 1, which indicates that growth in height is higher than in diameter, not supporting the second expectation. These results show that life strategies in shade-tolerant species may imply in more trade-off combinations than previously described.
Foram testadas duas hipóteses relativas a espécies florestaistolerantes à sombra em uma população de Rudgea parquioides, um arbusto característico do sul do Brasil: 1) espécies tolerantes à sombra possuem uma estrutura populacional composta por um grande número de indivíduos pequenos e 2) a alocação de biomassa para o crescimento em diâmetro é maior que para o crescimento em altura. Foram descritas as estruturas de tamanho (altura e diâmetro do tronco) e relações alométricas através da contagem e medição de todos os indivíduos de R. parquioides em uma área de 725m² no município de Curitiba (25"25'S; 49"19'W). Um total de 916 indivíduos(12.634 ind.ha-1) foi medido nesta área. A primeira hipótese foi aceita, uma vez que a distribuição em classes de altura e de diâmetro mostrou um predomínio de indivíduos pequenos (coeficiente de assimetria > 1). Por outro lado, a regressão entre altura e diâmetro na base do caule mostrou inclinação β < 1, o que indica que o crescimento em altura é maior que em diâmetro, não suportando a segunda hipótese. Esses resultados mostram que as estratégias de crescimento em espécies tolerantes à sombra podem implicar em outras relações ecológicas além das já descritas.
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Ecossistema , Rubiaceae/classificação , Árvores , Biomassa , Brasil , Rubiaceae/anatomia & histologia , Rubiaceae/crescimento & desenvolvimentoRESUMO
BACKGROUND: Schistosomiasis affects more than 200 million individuals worldwide, with a further 650 million living at risk of infection, constituting a severe health problem in developing countries. Even though an effective treatment exists, it does not prevent re-infection, and the development of an effective vaccine still remains the most desirable means of control for this disease. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we report the cloning and characterization of a S. mansoni Stomatin-like protein 2 (SmStoLP-2). In silico analysis predicts three putative sites for palmitoylation (Cys11, Cys61 and Cys330), which could contribute to protein membrane association; and a putative mitochondrial targeting sequence, similar to that described for human Stomatin-like protein 2 (HuSLP-2). The protein was detected by Western blot with comparable levels in all stages across the parasite life cycle. Fractionation by differential centrifugation of schistosome tegument suggested that SmStoLP-2 displays a dual targeting to the tegument membranes and mitochondria; additionally, immunolocalization experiments confirm its localization in the tegument of the adult worms and, more importantly, in 7-day-old schistosomula. Analysis of the antibody isotype profile to rSmStoLP-2 in the sera of patients living in endemic areas for schistosomiasis revealed that IgG1, IgG2, IgG3 and IgA antibodies were predominant in sera of individuals resistant to reinfection as compared to those susceptible. Next, immunization of mice with rSmStoLP-2 engendered a 30%-32% reduction in adult worm burden. Protective immunity in mice was associated with specific anti-rSmStoLP-2 IgG1 and IgG2a antibodies and elevated production of IFN-gamma and TNF-alpha, while no IL-4 production was detected, suggesting a Th1-predominant immune response. CONCLUSIONS/SIGNIFICANCE: Data presented here demonstrate that SmStoLP-2 is a novel tegument protein located in the host-parasite interface. It is recognized by different subclasses of antibodies in patients resistant and susceptible to reinfection and, based on the data from murine studies, shows protective potential against schistosomiasis. These results indicate that SmStoLP-2 could be useful in a combination vaccine.
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Antígenos de Helmintos/análise , Antígenos de Helmintos/imunologia , Proteínas de Helminto/análise , Proteínas de Helminto/imunologia , Schistosoma mansoni/química , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/genética , Clonagem Molecular , Feminino , Proteínas de Helminto/genética , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Interferon gama/metabolismo , Leucócitos Mononucleares/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Organelas/química , Esquistossomose mansoni/imunologia , Análise de Sequência de DNA , Fator de Necrose Tumoral alfa/metabolismo , VacinaçãoRESUMO
In this study, we have identified a secreted 13 kDa lectin from Mtb (Mtb, Mycobacterium tuberculosis; sMTL-13) by homology search of a non-redundant lectin database. Bioinformatic analysis revealed that sMTL-13 belongs to the ricin-type beta-trefoil family of proteins containing a Sec-type signal peptide present in Mtb complex species, but not in non-tuberculous mycobacteria. Following heterologous expression of sMTL-13 and generation of an mAb (clone 276.B7/IgG1kappa), we confirmed that this lectin is present in culture filtrate proteins from Mtb H37Rv, but not in non-tuberculous mycobacteria-derived culture filtrate proteins. In addition, sMTL-13 leads to an increased IFN-gamma production by PBMC from active tuberculosis (ATB) patients. Furthermore, sera from ATB patients displayed high titers of IgG Ab against sMTL-13, a response found to be decreased following successful anti-tuberculosis therapy. Together, our findings reveal a secreted 13 kDa ricin-like lectin from Mtb, which is immunologically recognized during ATB and could serve as a biomarker of disease treatment.
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Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Lectinas/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Sequência de Aminoácidos , Anticorpos Antibacterianos/genética , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Western Blotting , Humanos , Imunoglobulina G/imunologia , Imuno-Histoquímica , Lectinas/genética , Lectinas/metabolismo , Dados de Sequência Molecular , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/metabolismoRESUMO
The expectations that shade-tolerant forest species show 1) a population structure composed by a high amount of small individuals, and 2) biomass allocation for diameter higher than for height growth, were tested for Rudgea parquioides, a typical shrub in Southern Brazil. We described the size structure (height and stem diameter) and allometrical relations of a R. parquioides population by counting and measuring all the individuals in a 725m(2) area in the municipality of Curitiba (25°25'S; 49°19'W). A total of 916 individuals (12,634 ind.ha(-1)) were recorded in the area. The first expectation was supported, since distribution by height and diameter classes showed a predominance of small individuals (skewness coefficients > 1). On the other hand, the regression between height and stem base diameter showed slope ß < 1, which indicates that growth in height is higher than in diameter, not supporting the second expectation. These results show that life strategies in shade-tolerant species may imply in more trade-off combinations than previously described.
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Ecossistema , Rubiaceae/classificação , Árvores , Biomassa , Brasil , Rubiaceae/anatomia & histologia , Rubiaceae/crescimento & desenvolvimentoRESUMO
BACKGROUND: During its development, the parasite Schistosoma mansoni is exposed to different environments and undergoes many morphological and physiological transformations as a result of profound changes in gene expression. Characterization of proteins involved in the regulation of these processes is of importance for the understanding of schistosome biology. Proteins containing zinc finger motifs usually participate in regulatory processes and are considered the major class of transcription factors in eukaryotes. It has already been shown, by EMSA (Eletrophoretic Mobility Shift Assay), that SmZF1, a S. mansoni zinc finger (ZF) protein, specifically binds both DNA and RNA oligonucleotides. This suggests that this protein might act as a transcription factor in the parasite. METHODOLOGY/PRINCIPAL FINDINGS: In this study we extended the characterization of SmZF1 by determining its subcellular localization and by verifying its ability to regulate gene transcription. We performed immunohistochemistry assays using adult male and female worms, cercariae and schistosomula to analyze the distribution pattern of SmZF1 and verified that the protein is mainly detected in the cells nuclei of all tested life cycle stages except for adult female worms. Also, SmZF1 was heterologously expressed in mammalian COS-7 cells to produce the recombinant protein YFP-SmZF1, which was mainly detected in the nucleus of the cells by confocal microscopy and Western blot assays. To evaluate the ability of this protein to regulate gene transcription, cells expressing YFP-SmZF1 were tested in a luciferase reporter system. In this system, the luciferase gene is downstream of a minimal promoter, upstream of which a DNA region containing four copies of the SmZF1 putative best binding site (D1-3DNA) was inserted. SmZF1 increased the reporter gene transcription by two fold (p
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Proteínas de Helminto/metabolismo , Schistosoma mansoni/metabolismo , Esquistossomose mansoni/parasitologia , Fatores de Transcrição/metabolismo , Animais , Células COS , Núcleo Celular/metabolismo , Chlorocebus aethiops , Feminino , Proteínas de Helminto/genética , Humanos , Masculino , Ligação Proteica , Transporte Proteico , Schistosoma mansoni/genética , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/metabolismo , Fatores de Transcrição/genéticaRESUMO
Schistosomiasis continues to be a significant public health problem that affects 200 million people worldwide. This is one of the most important parasitic diseases, and one whose effective control is unlikely in the absence of a vaccine. In this study, we have isolated a cDNA clone encoding the Schistosoma mansoni Sm21.6 protein that has 45% and 44% identity with Sm22.6 and Sj21.7 EF-hand containing antigens, respectively. Confocal microscopy analysis revealed that Sm21.6 is a membrane-associated protein localized on the S. mansoni adult worm. Mouse immunization with rSm21.6 induced a mixed Th1/Th2 cytokine profile and no protection against infection. However, vaccination with rSm21.6 reduced by 28% of liver granuloma numbers, 21% of granuloma area and 34% of fibrosis. Finally, rSm21.6 was recognized by sera from individuals resistant to reinfection compared with patients susceptible to reinfection and this molecule should be further studied as potential biomarker for disease resistance. In conclusion, Sm21.6 is a new tegument protein from S. mansoni that plays an important role in reducing pathology induced by parasite infection.
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Antígenos de Protozoários/imunologia , Fígado/patologia , Proteínas de Protozoários/imunologia , Vacinas Protozoárias/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Animais , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/genética , Membrana Celular/química , Citocinas/metabolismo , Motivos EF Hand , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Proteínas de Protozoários/genética , Vacinas Protozoárias/genética , Esquistossomose mansoni/imunologia , Homologia de Sequência de Aminoácidos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate. METHODS AND FINDINGS: We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-gamma, TNF-alpha and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins. CONCLUSION: This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.
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Antígenos de Helmintos/imunologia , Proteínas de Helminto/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Células Th1/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/administração & dosagem , Antígenos de Helmintos/genética , Feminino , Proteínas de Helminto/administração & dosagem , Proteínas de Helminto/genética , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pulmão/imunologia , Pulmão/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Schistosoma mansoni/genética , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/parasitologia , Vacinas/administração & dosagem , Vacinas/genética , Vacinas/imunologiaRESUMO
Schistosomiasis continues to be a significant public health problem in tropical countries such as Brazil. Even though drug treatment in endemic areas has been shown to be efficient for controlling morbidity, it does not reduce prevalence due to constant reinfections. Therefore, a long-term disease control strategy is needed combining mass chemotherapy with a protective vaccine. Although the field of vaccine development has experienced more failures than successes, encouraging results have been obtained in recent years using defined recombinant derived Schistosoma mansoni antigens. This article primarily reviews the progress in the development of a vaccine against S. mansoni in Brazil. We discuss here different forms of vaccine tested in Brazil in pre-clinical trials and immunologic studies performed with patients in endemic areas of schistosomiasis. Lastly, we reviewed the S. mansoni genomic projects developed in the country and the recent advances in the identification of new molecules with potential as vaccine targets.
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Pesquisa , Schistosoma mansoni/imunologia , Esquistossomose/imunologia , Esquistossomose/prevenção & controle , Vacinas/imunologia , Animais , Antígenos de Helmintos/imunologia , Brasil , Genoma Helmíntico , Humanos , Schistosoma mansoni/genética , Vacinas Sintéticas/imunologiaRESUMO
Brucella species are important zoonotic pathogens affecting a wide variety of mammals. Therefore, the identification of new Brucella virulence factors is of great interest in understanding bacterial pathogenesis and immune evasion. In this study, we have identified Brucella abortus vacB gene that presents 2343 nucleotides and 781 amino acids and it shows 39% identity with Shigella flexneri vacB gene that encodes an exoribonuclease RNase R involved in bacterial virulence. Further, we have inactivated Brucella vacB by gene replacement strategy generating a deletion mutant strain. In order to test the role of Brucella vacB in pathogenesis, BALB/c and interferon regulatory factor-1 (IRF-1) knockout (KO) mice received Brucella vacB mutant, the virulent parental strain 2308 or the vaccine strain RB51 and the bacterial CFU numbers in spleens and mous survival were monitored. Our results demonstrated that the B. abortus DeltavacB mutant and the wild type strain 2308 showed similar CFU numbers in BALB/c mice. Additionally, IRF-1 KO mice that received either the vacB mutant or S2308 strain died in 12-14 days postinfection; in contrast, all animals that received the RB51 vaccine strain survived for 30 days postinoculation. In summary, this study reports that the vacB gene in B. abortus has no impact on bacterial pathogenesis.