ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6-specific nanobody restricts <i>M. tuberculosis</i> growth in macrophages.

ABSTRACT: Mycobacterium tuberculosis (Mtb) is known to survive within macrophages by compromising the integrity of the phagosomal compartment in which it resides. This activity primarily relies on the ESX-1 secretion system, predominantly involving the protein duo ESAT-6 and CFP-10. CFP-10 likely acts as a chaperone, while ESAT-6 likely disrupts phagosomal membrane stability via a largely unknown mechanism. we employ a series of biochemical analyses, protein modeling techniques, and a novel ESAT-6-specific nanobody to gain insight into the ESAT-6's mode of action. First, we measure the binding kinetics of the tight 1:1 complex formed by ESAT-6 and CFP-10 at neutral pH. Subsequently, we demonstrate a rapid self-association of ESAT-6 into large complexes under acidic conditions, leading to the

SUBMITTER: Bates TA 

PROVIDER: S-EPMC11132683 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature