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

Abstract
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.
AuthorsQinglan Wang, Helena I M Boshoff, Justin R Harrison, Peter C Ray, Simon R Green, Paul G Wyatt, Clifton E Barry 3rd
JournalScience (New York, N.Y.) (Science) Vol. 367 Issue 6482 Pg. 1147-1151 (03 06 2020) ISSN: 1095-9203 [Electronic] United States
PMID32139546 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Chemical References
  • Amides
  • Bacterial Proteins
  • Lipids
  • Sulfhydryl Compounds
  • phthiocerol dimycocerosate
  • Glucose
  • Glycerol
  • propionamide
Topics
  • Amides (metabolism)
  • Bacterial Proteins (genetics, metabolism)
  • Biological Transport
  • Cell Membrane (metabolism)
  • Cell Membrane Permeability
  • Drug Resistance, Bacterial (genetics)
  • Gene Deletion
  • Glucose (metabolism)
  • Glycerol (metabolism)
  • Lipids (chemistry)
  • Mycobacterium tuberculosis (drug effects, genetics, metabolism)
  • Sulfhydryl Compounds (chemistry, pharmacology)

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