Functional analysis of early secreted antigenic target-6, the dominant T-cell antigen of Mycobacterium tuberculosis, reveals key residues involved in secretion, complex formation, virulence, and immunogenicity
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The pathogenesis of Mycobacterium tuberculosis largely depends on the secretion of the 6-kD early secreted antigenic target ESAT-6 (EsxA) and the 10-kD culture filtrate protein CFP-10 (EsxB) via the ESX-1/typeVII secretion system. Although gene products fr ...
The clinical success of recombinant protein therapeutics in the treatment of disease is a hallmark of modern medical research, yet there remain numerous unaddressed issues regarding their delivery and immunogenicity. Regardless of in vivo efficacy, the bio ...
Vaccines aiming to activate cytotoxic T cells require cross-presentation of exogenous antigen by antigen-presenting cells (APCs). We recently developed a synthetic nanoparticle vaccine platform that targets lymph node-resident dendritic cells (DCs), capabl ...
During infection, most pathogenic bacteria deliver proteins to the host cell cytoplasm to manipulate host behavior. In this issue of Cell Host & Microbe, Spanò and colleagues describe a system where a bacterium produces an exotoxin while inside the host ce ...
Human TRIM5alpha restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5alpha that acquire the ability to inhibit B-MLV infection prior to reverse transcription without ...
ESAT-6 system 1 (ESX-1)-mediated secretion in Mycobacterium tuberculosis is dependent on proteins encoded by the cotranscribed espA-espC-espD gene cluster. While the roles of EspA and EspC with respect to the ESX-1 secretion system have been actively inves ...
The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4(+) T helper (Th) 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization ...
Owing to its highly immunodominant nature and ability to induce long-lived memory immunity, ESAT-6. a prominent antigen of Mycobacterium tuberculosis, has been employed in several approaches to develop tuberculosis vaccines Here, for the first time, we com ...
Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the ...
Background: The variable efficacy (0-80%) of Mycobacterium bovis Bacille Calmette Gurein (BCG) vaccine against adult tuberculosis (TB) necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG) over-expressing promisi ...