Investigation into the Roles of EsxA N-α-Acetylation in Pathogenesis of Mycobacterium tuberculosis and Potential Host-Binding Proteins
Abstract
EsxA (6-kDa early secreted antigenic target, ESAT-6) is a critical virulence factor of Mycobacterium tuberculosis (Mtb). EsxA is secreted in a heterodimer with EsxB (10-kDa culture filtrate protein, CFP-10) through the Type VII secretion system of Mtb, called ESX-1. The dissociation of EsxA and EsxB heterodimer (EsxA:B), upon acidification, is required for EsxA to penetrate into the phagosomal membranes, which has been implicated in Mtb translocation from the phagosome to the cytosol. However, the mechanism of EsxA:B dissociation is not clear. In this study, we investigated the role of N-α-acetylation of EsxA in the heterodimer dissociation, mycobacterial cytosolic translocation, and overall virulence as well. Our results have demonstrated that N-α-acetylation of EsxA is required for the dissociation of the heterodimer at acidic conditions, which facilitates the mycobacterial cytosolic translocation. Subsequently, we also tried to identify the potential acetyltransferase of EsxA by gene bank search and tested if RimI, a potential N-α-acetyltransferase, acetylates EsxA in vitro. However, our data suggests that RimI does not acetylate EsxA. Inspired by a recent finding that EsxA may interact with the host mitochondrial receptors prohibitin 1 and 2 (PHB1 and PHB2), which plays a role in Mtb-regulated autophagy, we initiated a new study to express and purify the PHB1/2 proteins and characterize their interactions with EsxA. In summary, the study has revealed the mechanism of N-α-acetylation of EsxA in Mtb virulence and built the basis for future studies of EsxA interactions with host factors.
Subject Area
Biology|Biochemistry|Microbiology
Recommended Citation
Aguilera, Javier, "Investigation into the Roles of EsxA N-α-Acetylation in Pathogenesis of Mycobacterium tuberculosis and Potential Host-Binding Proteins" (2023). ETD Collection for University of Texas, El Paso. AAI30488221.
https://scholarworks.utep.edu/dissertations/AAI30488221