ABSTRACT
AIMS: The importance of bacterioferritin in the virulence and pathogenicity of the genus Mycobacterium is still unclear. The aim of this study was to analyse if the expression of a recombinant bacterioferritin from M. tuberculosis (Mtb) by Mycma could improve the capacity of this bacillus to resist the host defence mechanisms. METHODS AND RESULTS: Recombinant Mycma, expressing bacterioferritin (Rv1876) from Mtb, was developed by transformation with pMIP12_Rv1876. To determine bacterioferritin influence on Mycma physiology and virulence, the mycobacteria growth was analysed in vitro and in vivo. It was observed that the expression of bacterioferritin improved the growth rate of recombinant Mycma_BfrA under iron excess and oxidative stress, as compared to the wild type. Furthermore, in the murine model of infection, it was observed that Mycma_BfrA-infected mice had higher bacillary load and a more pronounced lesion in the lungs when compared with the wild type. CONCLUSION: This study showed that bacterioferritin confers additional resistance to stress conditions, resulting in increased pathogenicity of Mycma during mice infection. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new insights about the importance of bacterioferritin in the virulence and pathogenicity of the Mycobacterium genus.
Subject(s)
Bacterial Proteins/metabolism , Cytochrome b Group/metabolism , Ferritins/metabolism , Mycobacterium abscessus/physiology , Mycobacterium abscessus/pathogenicity , Animals , Bacterial Load , Bacterial Proteins/genetics , Cytochrome b Group/genetics , Ferritins/genetics , Mice , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/pathology , Mycobacterium abscessus/genetics , Mycobacterium abscessus/growth & development , Mycobacterium tuberculosis/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Stress, Physiological , VirulenceABSTRACT
In an attempt to clarify the issue of genetic predisposition to leprosy, we examined the distribution of class II human leucocyte antigen variants (DR and DQ) in 70 patients from around the city of Goiânia, Brazil. Only two of the patients presented the tuberculoid form of the disease, whereas 17 fell into the lepromatous category; 51 were intermediate. The allele frequencies found were compared with those in a group of 77 healthy controls. We found an increased frequency of the HLA-DRB1*11 allele in patients with lepromatous leprosy compared with healthy controls (P=0.0132; RR=4.130, 95% Cl: 1.338 to 12.747). These results suggest that the DRB1*11 allele could be related with susceptibility to lepromatous leprosy in Brazil.
Subject(s)
Alleles , Gene Frequency , Histocompatibility Antigens Class II/genetics , Leprosy/genetics , Adult , Brazil , Female , Gene Frequency/genetics , Genetic Predisposition to Disease , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: CD8+ and natural killer (NK) cells have been considered the most effective cells in the combat of cancer, contributing to better prognosis and longer survival. METHODS: The aim of this study was to evaluate the population of CD8+ and NK cells, by immunohistochemistry, in samples of oral cavity squamous cell carcinoma (OCSCC) and lip squamous cell carcinoma (LSCC), leukoplakia, actinic cheilitis, and healthy oral mucosa (control). The relationship of CD8+ and NK cells with survival data, lymph node metastasis, tumor size, and proliferative index was also evaluated. RESULTS: The number of peritumoral and intratumoral CD8+ and NK cells was significantly higher in LSCC, when compared with control, pre-malignant lesions, and OCSCC. A higher proportion of peritumoral CD8+ cells demonstrated correlation with a lower neoplastic proliferative index. Moreover, patients with OCSCC with a high density of peritumoral CD8+ cells showed a tendency towards a longer survival time. CONCLUSIONS: The differential CD8+ and NK cells infiltration in oral SCC might reflect a distinctive tumor microenvironment with a favorable local cytotoxic immune response against neoplastic cells.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Carcinoma, Squamous Cell/immunology , Killer Cells, Natural/immunology , Lip Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Mouth Neoplasms/immunology , CD8-Positive T-Lymphocytes/pathology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/secondary , Cheilitis/immunology , Cheilitis/pathology , Cyclin B1/analysis , Female , Follow-Up Studies , Humans , Immunohistochemistry , Killer Cells, Natural/pathology , Leukoplakia, Oral/immunology , Leukoplakia, Oral/pathology , Lip Neoplasms/pathology , Lymphatic Metastasis/pathology , Lymphocyte Count , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Mitotic Index , Mouth Mucosa/immunology , Mouth Mucosa/pathology , Mouth Neoplasms/pathology , Neoplasm Invasiveness , Neoplasm Staging , Survival RateABSTRACT
A group of Brazilian leprosy patients and controls were genotyped for a CA-repeat microsatellite polymorphism within the interferon (IFN)-gamma gene. A significantly higher frequency of alleles 5-7 was observed in this patient population, indicating that IFN-gamma gene polymorphism may contribute to the course of leprosy post-infection.
Subject(s)
Gene Frequency , Interferon-gamma/genetics , Leprosy/genetics , Microsatellite Repeats , Brazil , Genetic Predisposition to Disease , Humans , Monte Carlo MethodABSTRACT
A group of Brazilian leprosy patients and controls were genotyped for a CA-repeat microsatellite polymorphism within the interferon (IFN)-gamma gene. A significantly higher frequency of alleles 5-7 was observed in this patient population, indicating that IFN-gamma gene polymorphism may contribute to the course of leprosy post-infection.
Subject(s)
Leprosy , Leprosy/classification , Leprosy/diagnosis , Leprosy/ethnologyABSTRACT
The effect of carbon sources on the level of beta-1,3-glucanases in the culture filtrates of Trichoderma harzianum (Tc) was investigated. Enzyme activity was detected in all carbon sources, but highest levels were found when laminarin and purified cell walls were used. Three isoforms of beta-1,3-glucanase were produced during growth of the fungus on purified cell walls. Two isoforms were produced on chitin, chitosan, N-acetylglucosamine and laminarin, while only one was detected when the fungus was grown on cellulose and glucose. A 36-kDa beta-1,3-glucanase (GLU36) was secreted from T. harzianum (Tc) grown on all carbon sources tested as demonstrated by Western blot analysis. We found that a significant increase in the level of GLU36 in the culture filtrate follows glucose exhaustion, suggesting that this enzyme is controlled by carbon catabolite repression.
