The conical shape of DIM lipids promotes Mycobacterium tuberculosis infection of macrophages.

ABSTRACT: Phthiocerol dimycocerosate (DIM) is a major virulence factor of the pathogen Mycobacterium tuberculosis (Mtb). While this lipid promotes the entry of Mtb into macrophages, which occurs via phagocytosis, its molecular mechanism of action is unknown. Here, we combined biophysical, cell biology, and modeling approaches to reveal the molecular mechanism of DIM action on macrophage membranes leading to the first step of Mtb infection. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry showed that DIM molecules are transferred from the Mtb envelope to macrophage membranes during infection. Multiscale molecular modeling and ³¹P-NMR experiments revealed that DIM adopts a conical shape in membranes and aggregates in

SUBMITTER: Augenstreich J 

PROVIDER: S-EPMC6926010 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature