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

Qinglan WangHelena I. M. BoshoffJustin R. HarrisonPeter C. Ray, Simon R. Green, Paul G. Wyatt, Clifton E. Barry III.

Science  06 Mar 2020: Vol. 367, Issue 6482, pp. 1147-1151
DOI: 10.1126/science.aav5912


Mycobacterium tuberculosis has an unusual outer membrane that lacks canonical porin proteins for the transport of small solutes to the periplasm. We discovered that 3,3-bis-di(methylsulfonyl)propionamide (3bMP1) inhibits the growth of M. tuberculosis, and resistance to this compound is conferred by mutation within a member of the proline-proline-glutamate (PPE) family, PPE51. Deletion of PPE51 rendered M. tuberculosis cells unable to replicate on propionamide, glucose, or glycerol. Growth was restored upon loss of the mycobacterial cell wall component phthiocerol dimycocerosate. Mutants in other proline-glutamate (PE)/PPE clusters, responsive to magnesium and phosphate, also showed a phthiocerol dimycocerosate–dependent growth compromise upon limitation of the corresponding substrate. Phthiocerol dimycocerosate determined the low permeability of the mycobacterial outer membrane, and the PE/PPE proteins apparently act as solute-specific channels.