secretory system in tb

Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, is one of the most successful pathogens in human history. An extremely resilient cell wall and highly evolved and coordinated strategies for immune evasion have made it a very formidable pathogen. The secretory proteins of M. tuberculosis play a crucial role in its virulence and immune evasion. The secretory proteins are secreted through tightly regulated secretion systems and modulate the host immune responses through a plethora of strategies, including epigenetic reprogramming of infected cells, targeting antigen presentation, inhibition of phagosomal maturation, modulation of cytokine production, apoptosis and redox regulation, etc...

Nontuberculous mycobacterial (NTM) pulmonary disease (PD) disproportionately affects otherwise healthy, older, Caucasian females. The reasons behind this are likely multifactorial involving several conspiring factors. A variety of factors are thought to contribute to increased susceptibility to NTM in the older adult including exposure to various environmental conditions and contaminants across the lifespan, genetic risk factors, hormonal changes, and immunodeficiency. Independent of sex and ancestry, respiratory muscle atrophy intensifies with age and an aging immune system can show functional decline of macrophages, poor lung migration and homing of dendritic cells, promotion of aberrant pro-inflammatory responses, acceleration of inflammation related to aging, and increased immunosenescence...

Adipocytokines are the major secretory products of adipose tissue and potential markers of metabolism and inflammation. However, their association in host immune response against tuberculous lymphadenitis (TBL) disease is not known. Thus, we measured the systemic levels of adipocytokines in TBL (n = 44) and compared to pulmonary tuberculosis (PTB, n = 44) and healthy control (HC, n = 44) individuals. We also examined the pre and post-treatment adipocytokine levels in TBL individuals upon completion of standard anti-tuberculosis treatment (ATT)...

The signal recognition particle (SRP) system plays an imperative role in transporting the secretory protein to its intended location. The SRP pathway running in Mycobacterium tuberculosis constitutes FtsY (signal receptor), FfH (SRP), and 4.5S RNA in which signal receptor acts in the GTP-dependent manner. In this study, we are rendering the essential facts of FtsY with respect to mycobacterial growth. The growth study experiment showed that downexpressed FtsY slowed the growth of Mycobacterium smegmatis mc2 155 from the initial lag phase to stationary phase...

The 38 kDa protein is a major antigen of mycobacterium tuberculosis and has been widely used in TB serodiagnosis, due to its highly sensitivity and specificity. Here we attempt to establish a production platform of recombinant 38 kDa protein in mammalian cells and to evaluate the potential value of 38 kDa protein in TB serodiagnosis. The 38 kDa gene is synthesized and cloned into a lentiviral expressing vector. Recombinant lentiviral vector LV-CMV-38 kDa-eGFP was packaged, titered, and then transduced into HEK 293 T cells...

Mycobacterium tuberculosis ( M. tb ) is an intracellular pathogen that exploits moonlighting functions of its proteins to interfere with host cell functions. PE/PPE proteins utilize host inflammatory signaling and cell death pathways to promote pathogenesis. We report that M. tb PE6 protein (Rv0335c) is a secretory protein effector that interacts with innate immune toll-like receptor TLR4 on the macrophage cell surface and promotes activation of the canonical NFĸB signaling pathway to stimulate secretion of proinflammatory cytokines TNF-α, IL-12, and IL-6...

A rise in drug-resistant tuberculosis (TB) cases demands continued efforts towards the discovery and development of drugs and vaccines. Secretory proteins of Mycobacterium tuberculosis (H37Rv) are frequently studied for their antigenicity and their scope as protein subunit vaccines requires further analysis. In this study, Rv3899c of H37Rv emerges as a potential vaccine candidate on its evaluation by several bioinformatics tools. It is a non-toxic, secretory protein with an 'immunoglobulin-like' fold which does not show similarity with a human protein...

The PE/PPE proteins encoded by seven percent (7%) of Mycobacterium tuberculosis (Mtb) genome are the chief constituents to pathogen's virulence reservoir. The fact that these genes have evolved along ESX secretory system in pathogenic Mtb strains make their investigation very intriguing. There is lot of speculation about the prominent role of these proteins at host pathogen interface and in disease pathogenesis. Nevertheless, the exact function of PE/PPE proteins still remains a mystery which calls for further research targeting these proteins...

Whole genome sequencing (WGS) is one of the most reliable methods for detection of drug resistance, genetic diversity in other virulence factor and also evolutionary dynamics of Mycobacterium tuberculosis complex (MTBC). First-line anti-tuberculosis drugs are the major weapons against Mycobacterium tuberculosis (MTB). However, the emergence of drug resistance remained a major obstacle towards global tuberculosis (TB) control program 2030, especially in high burden countries including Pakistan. To overcome the resistance and design potent drugs, genomic variations in drugs targets as well as in the virulence and evolutionary factors might be useful for better understanding and designing potential inhibitors...

Introduction: The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK. Materials and Methods: Blood samples were obtained from BCG-immunized infants of mothers with ( n = 110) and without ( n = 121) latent Mycobacterium tuberculosis infection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI ( n = 25) in the UK at 10 and 52 weeks after birth...

Acanthamoeba is an opportunistic protozoan pathogen which is found in diverse environment worldwide. Being ubiquitous nature of this amoeba we come across it in our daily life. Acanthamoeba species are recognized as human pathogens; that may cause blinding keratitis and rare but fatal granulomatous encephalitis involving central nervous system. To date, there is not a single report in literature demonstrating anti-Acanthamoeba antibodies among the Saudi population, and thus aim of the present study. Using ELISA, we identified the antibody level in the local population...

The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) stains has escalated the need for developing more efficient drugs and therapeutic strategies against tuberculosis. Here we functionally annotate a secretory mycobacterial asparaginase Rv1538c (MtA) and describe its biochemical properties. MtA primarily existed as dimer along with a minor population of multimers. Circular dichroism and fluorescence spectroscopy demonstrated a compact structure in Tris HCl buffer at pH 8.0. Under these conditions it also displayed optimum activity...

Tumor-derived extracellular vesicles (EVs), as tumor vaccines, carry tumor-associated antigens (TAAs), and were expected to transfer TAAs to antigen-presenting cells. However, treatment with tumor-derived EVs exhibited no obvious antitumor effect on the established tumors, likely due to their immuno-suppressive functions, and also to the poor immunogenicity of TAAs. In order to improve the immune stimulating properties, EVs expressing a highly immunogenic bacterial antigen, 6 kDa early secretory antigenic target (ESAT-6), from Mycobacterium tuberculosis were prepared by genetically modifying the parent tumor cells with a plasmid coding for ESAT-6...

Tuberculosis (TB) is believed to be one of the leading causes of death in the world; nevertheless, Bacillus Calmette-Guérin (BCG) is the solitary vaccine utilized to prevent TB. Despite the protective effect of this vaccine in children, its efficiency remains under question in adults. We conducted the present study to provide an overview of DNA based vaccines against TB and highlight the vaccine delivery advances and limitations. This study also aimed to bring a review of mycobacterial antigens, including heat shock protein 65 (Hsp65), antigen 85A (Ag85A), early secretory antigenic target 6 (EAST-6), antigen 85B (Ag85B), and heat shock protein X (HspX) as the most extensively considered antigens in the development of vaccines against M...

Mycobacterium tuberculosis, the causative agent of Tuberculosis has plagued humankind for ages and has surfaced stronger than ever with the advent of drug resistance. Mycobacteria are adept at evading the host immune system and establishing infection by engaging host factors and secreting several virulence factors. Hence these secretion systems play a key role in mycobacterial pathogenesis. The type VII secretion system or ESX (early secretory antigenic target (ESAT6) secretion) system is one such crucial system that comprises five different pathways having distinct roles in mycobacterial proliferation, pathogenesis, cytosolic escape within macrophages, regulation of macrophage apoptosis, metal ion homeostasis, etc...

Introduction  Otitis media (OM) is considered one of the most common reasons patients seek medical care in childhood. The fluctuating nature of hearing loss in cases of OM leads to irregular sound stimulation of the central auditory nervous system. Objectives  To analyze the long-latency auditory-evoked potential (LLAEP) by verbal and nonverbal sounds in children with a history of OM in the first six years of life. Methods  A total of 106 schoolchildren participated in the study, 55 females and 51 males, aged between 8 and 16 years, who were divided into 3 groups: the control group (CG), the bilateral experimental group (BEG), and the unilateral experimental group (UEG)...

Objective: To verify the secretory ability of the hypoxic response protein 1 (HRP1) encoded by Mycobacterium tuberculosis (Mtb) Rv 2626 c . Methods: The target gene attached with His tag was amplified from the genome of Mtb standard virulence strain H37Rv. The recombinant plasmid contained the above amplified product was constructed and electroporated into Mycobacterium smegmatis (Ms) (MC 2 155) to construct a recombinant strain. Protein expression was induced under heat condition, and the expression of protein from the culture filtrates and the bacterial lysates was detected afterward...

Objectives: Mycobacterium tuberculosis is the causative organism of tuberculosis, which is the most lethal disease after cancer in the current decade. The development of multidrug and broadly drug-resistant strains is making the problem of tuberculosis more and more critical. In the last 40 years, only one molecule has been added to the treatment regimen. Generally, drug design and development programs target proteins whose function is known to be essential to the bacterial cell. M. tuberculosis possesses specialized protein export systems like the SecA2 export pathway and ESX pathways...

Mycobacterium tuberculosis ( M. tuberculosis ) is the causative agent of tuberculosis in human. One of the major M. tuberculosis virulence factors is early secretory antigenic target of 6-kDa (ESAT-6), and EccB5 protein encoded by eccB5 is one of its components. EccB5 protein is a transmembrane protein in ESX-5 system. The aim of this study is to explore the characteristics of wild-type EccB5 and its mutant form N426I. We expressed the EccB5 protein by cloning the mutant and wild-type eccB5 gene in Escherichia coli ( E...

Virulent Mycobacterium tuberculosis (MTB) strains cause cell death of macrophages (Mϕ) inside TB granuloma using a mechanism which is not well understood. Many bacterial systems utilize toxins to induce host cell damage, which occurs along with immune evasion. These toxins often use chameleon sequences to generate an environment-sensitive conformational switch, facilitating the process of infection. The presence of toxins is not yet known for MTB. Here, we show that MTB-secreted immunogenic MPT63 protein undergoes a switch from β-sheet to helix in response to mutational and environmental stresses...