Nα-Acetylation of Virulence Factor EsxA of Mycobacterium tuberculosis Causes It to Dissociate from Its Chaperone EsxB; This Dissociation Is Known to Enable EsxA Membrane Permeabilization and Mycobacterial Cytosolic Translocation and Virulence

Biology students and faculty members from The University of Texas at El Paso (UTEP) have discovered a new target for tuberculosis drug development. Their study was published in the April 24, 2020 issue of the Journal of Biological Chemistry, a publication of the American Society of Biochemistry and Molecular Biology (ASBMB). The article is titled “Nα-Acetylation of the Virulence Factor EsxA Is Required for Mycobacterial Cytosolic Translocation and Virulence.” Jianjun Sun, PhD, Associate Professor in UTEP's Department of Biological Sciences, led the research on Mycobacterium tuberculosis (Mtb), the bacterial pathogen that causes tuberculosis (TB). TB is one of the leading infectious diseases in the world. Development of novel therapeutics against TB is urgently needed. Dr. Sun's lab has been investigating the mechanisms of Mtb pathogenesis for more than 10 years at UTEP, with a specific focus on EsxA, which is a virulence factor essential for Mtb virulence and a preferred target for developing novel anti-TB drugs and vaccines. During infection, Mtb is "eaten up" by human immune cells. Normally, bacteria are killed within the immune cells, but Mtb releases virulence factors, such as EsxA, to disarm the host's immune defense. The study discovered that the Nα-acetylation of EsxA can drastically affect the course of the infection. "This research was technically challenging, but the students were able to overcome the challenges and accomplished the goals," Dr. Sun said.
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