PE/PPE proteins mediate nutrient transport across the outer membrane of Mycobacterium tuberculosis

Abstract

Porin' through the wax Mycobacterium tuberculosis has a distinctive physiology that allows it to persist in the human body, including a wax-like cell coat that is largely impermeable and can resist attack by host immune response effectors. Wang et al. identified a simple molecule that effectively crosses this cell coat and kills M. tuberculosis cells. Whole-genome sequencing of mutants resistant to this molecule, 3,3- bis -di(methylsulfonyl)propionamide, showed scattered mutations in a protein called PPE51, and these mutants resulted in a spectrum of nutrient-related growth defects. Experiments suggest that PE/PPE family proteins are small molecule–selective channels analogous to outer membrane porins, which allow M. tuberculosis to take up nutrients while maintaining an otherwise impermeable barrier. Science , this issue p. 1147