Abstract
As a major effector of the ESX-1 secretion system, EsxA is essential for the virulence of pathogenic mycobacteria, such as Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm). EsxA possesses an acidic pH-dependent membrane permeabilizing activity and plays an essential role by mediating mycobacterial escape from the phagosome and translocation to the cytosol for intracellular replication. Moreover, EsxA regulates host immune responses as a potent T-cell antigen and a strong immunoregulator. EsxA interacts with multiple cellular proteins and stimulates several signal pathways, such as necrosis, apoptosis, autophagy, and antigen presentation. Interestingly, there is a co-dependency in the expression and secretion of EsxA and other mycobacterial factors, which greatly increases the complexity of dissecting the precise roles of EsxA and other factors in mycobacterium–host interaction. In this review, we summarize the current understandings of the roles and functions of EsxA in mycobacterial infection and discuss the challenges and future directions.
Highlights
Cells 2021, 10, 1645. https://doi.org/Mycobacterium is a genus that consists of at least 188 different species [1,2,3,4]
The molecular dynamics (MD) simulation shows that the acetylated N-terminal arm of EsxA makes direct contracts with EsxB in a frequent “bind-and-release” mode, which generates a force of 44 pN to pull
Instead of causing cytolysis, the exogenously added EsxA protein without ASB-14 is internalized into the lung epithelial cells and traffics to acidic subcellular compartments, where it inserts into the membranes [188]
Summary
Mycobacterium is a genus that consists of at least 188 different species [1,2,3,4]. Several of them, especially Mycobacterium tuberculosis (Mtb), are imposing a great threat to public health due to their strong virulence and pathogenicity to humans [5,6,7,8,9,10,11,12]. Hundreds of genes necessary for Mtb intracellular survival have been identified [6,20,21,22,23,24,25]. Among these genes, EsxA (6 kDa early secreted antigenic target, ESAT-6) and EsxB (10 kDa culture filtrate protein, CFP-10) have drawn much attention for their essential roles in. Mtb infection [41], and gene deletion or the impaired secretion of EsxA leads to reduction in Mtb intracellular survival [28,29,30,42], which implicates EsxA as playing an essential role in Mtb virulence.
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