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Cellular mechanisms of the virulence of Mycobacterium tuberculosis
Tuberculosis is a chronic pulmonary infection caused by mycobacterium tuberculosis being one of the main public health problem, MTB has caused 9, 6 million active TB infections, it is a bacteria carrying a wide range of virulence factorswhich are primarily at the level of their cell wall by means of these are enabled to penetrate and multiply intracellularly and this will allow itreactivate later due to its abnormal reaction of the organism producing the rejection of a substance that the guest develops. At present it is said that there is a new Virulence Factor ESAT – 6 which is produced by MTB important for its pathogenesis.
M. Tuberculosis produces most clinical pictures and is the most crucial from the pathogenic and health perspective. It is an ancestral, infectious, chronic and large extent is lethal;It is estimated that it is a complex of microbiological and immunological phenomena is classified among the most significant infectious diseases of our times. Mycobacteriaceae family, Actinomycetaceae order. These organisms will present unstable bacillary -looking morphology, slightly curved or cocoids, do not form spores, flagella, or capsules despite the fact that a layer of glycopeptidolipids similar to a capsule has been specified similar to a capsule. They measure 0.2 to 0.6 um diameter by 1.0 to 10.0 um long, when filamentous fragments presents that due to their movement they fragment. They are considered as acid resistant alcohol bacilli (BAAR) this means due to their high lipid content in their cell wall. This occurs at its tintorial base occasionally staining with the staining of Gram, however they are determined as weak gram, we find three elements that make up the named Core or center of the cell wall of M. Tuberculosis: mycolic acid that is covalently detected to Arabinogalactana, which simultaneously relates to the peptidoglucano, sensitive to lactamic β β.
As mycobacterium tuberculosis (MTB) has previously detailed, it is the primary infectious disease in the world, so the MTB invades the human host by aerosol and establishes an infection in the lung through the use of virulence factors to combat host immunity. There is currently a new role known as the ESAT – 6 virulence factor intervenes in the regulation of ESAT – 6Fagosomic rupture, microbacterial cytolesis, translocation and cell to cell propagation. ESAT – 6 can function as a substantial modulator of the inflammatory responses of the host when manipulating several intracellular signaling paths in macrophages, T cells and epithelial cells, then the new role of the ESAT – 6 is informed in the differentiation and polymerization of Macrophages, it was discovered that during early infection the differentiation of macrophages MO and M2 towards the pro inflammatory phenotype to execute the formation of granulomas which are a mass of immune cells that forms when the immune system tries to isolate strange substances that have been Unable to eliminate, then ESAT – 6 I channel the change of phenotype m1 proinflamatory m1 (which have bactericidal functions) to antinflammatories m2 are those that are activated alternately are involved in the resolution of inflammation and healing of the tissue to maintain the infection During the subsequent persistent phases.
Finally, when the viable bacillus is phagocyted by MA, it displays its pathogenic capacity 6 KDA (Early Secretory Antigenic Target) ESAT -6 is an indispensable peptide to avoid the union of phage. In this way the bacillus uses its multiplication capacity to the maximum is a single alveolar macrophage (MA) with proximity between 5 to 6 cycles of the division to achieve a concentration between 32 and 64 bacilli this process evolves along about 5 to 6days inferring that each division cycle in m.Tuberculosis requires about 24h raising ma, which bacilli are transformed again and are again phagocyted by the MA from the interstitial space that replaces the necrossed. This process is reacted once again causing at least up to 1.000 bacilli causing enough generation of
Quimocins (small proteins, secreted by cells that modulate the immune system) by the MA infected to produce an inflammatory response. With the inflammation, the balance is fractioned when a liquid is generated at the capillary level that ends the alveolus tightness and allows the entry of polymorphonuclear cells (PMN) commonly neutrophils and monocytes that will depend on the type of chitosine or cytosine sneakers secreted by the MA at the same time allowsA more energetic washing of the affected alveoli draining towards the lymphatic nodules by means of the afferent lymph capillaries in this way is how m. Tuberculosis infects first to nodule macrophages causing lymphadenitis, and dendritic cells.
Then the 6KD have an antigenic objective secreted by MTB that inhibits the proliferation and differentiation of peripheral blood CD34 cells through the system that we have previously named ESAT – 6 specific. The elimination of the ESX – 1 genes that implies substrate genes Esx – 1 ESAT – 6 and culture filtering protein This ESAT gene only makes the MTB less pathogenic, despite the biological activity of ESAT – 6In terms of bacterial physiology and pathogenesis of MTB it is still uninquented, in addition to being demonstrated that it induces a lysis, it refers to the deterioration of pulmonary epithelial cells due to an injury to its plasma membrane and macrophage apoptosis. Several studies with ESAT – 6 have shown that it has the potential to handle human protective immune responses against tuberculosis infection therefore ESAT – 6 can play an immune role in the evasion of MTB. To test the potential role of esat – 6 in abnormal hematopoiesis of tuberculosis infection as mentioning, they have examined esat – 6 in human hematopoietic cells using CD34 + cells + the results showed that ESAT – 6 inhibits the proliferation and differentiation of theCD34 + cells for the induction of a complete HPC DXF supplement this will generate an immune response to a hostile agent which will allow sufficient expansion of cells. Then MTB -secreted proteins have a critical role by manipulation of human immune cells at the beginning of tuberculosis pathology in the early phase of active infection due to which the secretion of ESAT – 6 per MTB passes through aSYSTEM SECRECION ESX – 1 Specific that is an essential virulence factor for MTB pathogenesis, this gene presents some importance in the development of abnormal hematopoiesis of patients with tuberculosis is commonly reflected by abnormal changes in blood cell reunion. There is a mutation in the phop gene that interferes with the ESX -1 secretion system that inhibits the secretion of ESAT -6, so here a totally different regulator is identified that involves PHOP and the ESPR transcription regulator in the transcriptional control of the transcriptional control of the OPACE OPACE that requires for the secretion of ESAT – 6 dependent on ESX – 1 although both regulators are able to influence the secretion of ESAT – 6 dependent on ESX – 1 although both regulators are able to influence the expression of Espace, it is shown that the Activation of the same requires a direct replacement of PHP and ESP in the promoter of SPAC Based on these results, they propose that a model that suggests such as protein – PHOP -SPR interactions contribute to the activation of space expression and in turn C They ontrole the secretion of ESAT – 6 An essential pathogenic determinant of MTB these results have significant implications in the mechanism of regulation of the virulence of M. Tuberculosis has been included in most of the MSX 1 -dependent modulations of the host cell defense and are then considered essential for virulence consistently, the elimination of locus esx -1 cancels the pending secretion of ESX -1
Proteins secreted by Mycobacterium tuberculosis, the agents causing tuberculosis, have gained greater attention in recent years as candidates for vaccines and as virulence factors some of the proteins such as the genetic antigen early objective is at – 6 and filtering cultureof the protein – 10 of the host is encoded by the region RD – 1 of m (cfp) 5.6 genome, the pathological distinctive seal of the tuberculosis response to m. tuberculosis is granuloma. Which is a spherical mass of immune cells which is formed when the immune system tries to isolate strange substance which has been unable to remove where T cells and macrophages interact with the extracellular matrix (ECM) to control the infection. The replacement of immune cells, including macrophages within the granuloma, depends on their adhesion to ECM, macrophages use integrins to adhere to FN a main ECM component. Integrins comprise a large group of heterodimeric transmembrane molecules that consist of subunits A and B united covalently among the 24 pairs of integrins identified in mammals so far, it is considered that monocytes/ macrophages express three integrins of the B1 family, it has been presentedThat the ligation and the grouping of integrins in the phagocytic cells activate the cytoplasmic kinase, which in turn leads to the activation of the phosphatodilinotisol signaling – 3 – kinase, the phospholipase c, d and the kinase protein c. These collective and highly regulated events control the ranges of the back of the cytoskeleton, the formation of focal contact that are transmembrane binding proteins through their intracellular domain bind to anchor proteins and through extracellular domain interact with the extracellular matrix anotherof ranges is cell mobility and cell survival and the synthesis of inflammatory mediators by phagocytical cells. ESAT – 6 and CFP – 10 (Culture filter protein 10) which are encoded by the RD1 region. ESAT – 6 is a powerful T antigen of T cells and is suggested as a diagnostic biomarker for TB infection and is used in immunoenzyme test;Recently fragments technology are small protein with the ability to join an antigen of natural antibodies.
Phylogenetically the genus Mycobacterium is within the Actinobacteria edge, with the generos Corynebacterium and Streptomyces as close relatives. The majority of approximately 130 defined mycobacteria species contain harmless saprophytes which indicates that they are nourished from waste from other organisms, the large rapid micobacteria group includes very few pathogenic species such as Mycobacterium Abscessus – Mycobacterium Bolletti. The latter mycobacteria represent emerging opportunistic pathogens that are recognized each time as agents causing acute and persistent pulmonary infections with cystic fibrosis, in addition, virulent models of animal infection have serious difficulties for human treatment due to their extensive level of medication resistance. Unlike the mycobacteria of rapid growth phylogenetically more diversified the mythly growth mycobacteria foran a subgroup in the phylogenetic tree based on 16s RNA and it is known that they house important human pathogens such as Mycobacterium leprae and also a series of opportunistic human pathogens, such as Mycobacterium marinumthat is considered close relative of M. Tuberculosis In general, it is considered that mycobacteria are gram positive bacteria, unlike other species that do not have an external membrane, mycobacteria have a lipid -rich cell wrapping that contains a standard internal membrane and an external membrane in particular called Mycomembrane, whichIt is specific to mycobacteria and could fulfill a barrier function similar to the outer membrane of gram negative bacteria.
M. Tuberculosis It is said that macrophage can penetrate through nonspecific phagocytosis by means of a series of well -defined receptors such as FCC, CR1, CR2, CR3 and Lectinas, FCC recognizes the bacteria covered with immunoglobulin g (IgG) that induces theOPSSONIZATION which is the process by which a pathogen is marked for ingestion and destruction by a phagocyte. Meanwhile CR3 recognizes the bacterium covered with C3BI that promotes the introduction to the macrophagous body without pseudopod formphosphatidil – inositol – hands of the adhesives authorizing the macrophage union.
The ability of microorganisms to survive within the macrophage needs the expression of a series of genes that translate into protein groups involved in the host relationship, among them we find cellular wrap and secretion such as surface components, enzymesof metabolism and those involved in the capture of metals. The tissue destruction produced by cell hypersensitivity is induced by m. Tuberculosis, in actulity no endotoxin (LPS) similar to gram negative bacteria has been found, in its cell wall there are components involved in the damage to the patient as micolic acids, among others.
The evidence proposes that microbial pathogens have the ability to boost genetic alterations in the host, such as the different mycobacterium tuberculosis studies as an etiological agent of the TB infection can arouse total alternations in the host for its survival by the Methyl DNA transfer, encoding genesas RV1988 during infection. The host -driven epigenetic change is a primary epigenetic mechanism that can modulate the immune response of the host, by inhibiting the expression of genes involved in the immune responses of the host. The fundamental role of the Toll 2 (TLR2) and (TLR4) receptor in the innate immune recognition and the MTB infection response is very well documented, also the methylation role of the in TLR2 raises potential changes in the immune response of the guest againstPulmonary tuberculosis.
Methyl acyl enzyme fundamental transfer in tuberculosis The results of genetic expression. Finally, the results of relative expression were compared together (XDR and sensitive) and fold changes were calculated. It was executed through the Kruskal – Wallis test this refers to a non -parametric method to test if a data group comes from the same population. The value p < 0.05 fue considerado como el nivel de significancia por lo cual los resultados mostraron que la expresión del gen Rv1988 aumentó significativamente en las cepas XDR Mtb en comparación con las cepas susceptibles.
In general it is considered that this tuberculosis disease is an emergency of public health worldwide, it is importantEssential to know it for a better study of the pathogenesis of the MTB, finally it is said that this ESAT – 6 gene intervene in the differentiation and polymerization of macrophages. It was also announced about the expression of a gene called RV 1988 is called a fundamental enzyme in tuberculosis and the results of genetic expression.
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