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

• Published in: Science (American Association for the Advancement of Science) Vol. 367; no. 6482; pp. 1147 - 1151
• Main Authors: Wang, Qinglan, Boshoff, Helena I M, Harrison, Justin R, Ray, Peter C, Green, Simon R, Wyatt, Paul G, Barry, 3rd, Clifton E
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 06.03.2020
• Subjects: Amides - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological Transport; Cell Membrane - metabolism; Cell Membrane Permeability; Cell walls; Channels; Clonal deletion; Drug Resistance, Bacterial - genetics; Gene Deletion; Gene sequencing; Genomes; Glucose - metabolism; Glycerol; Glycerol - metabolism; Immune response; Lipids - chemistry; Magnesium; Membrane permeability; Membranes; Mutants; Mutation; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; Nutrient transport; Nutrients; Periplasm; Phthiocerol dimycocerosate; Porins; Proline; Protein transport; Proteins; Solutes; Substrates; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - pharmacology; Transport; Tuberculosis; Waxes; Whole genome sequencing
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aav5912

has an unusual outer membrane that lacks canonical porin proteins for the transport of small solutes to the periplasm. We discovered that 3,3- -di(methylsulfonyl)propionamide (3bMP1) inhibits the growth of , and resistance to this compound is conferred by mutation within a member of the proline-proline-glutamate (PPE) family, PPE51. Deletion of PPE51 rendered 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.