PE/PPE proteins mediate nutrient transport across the outer membrane of Mycobacterium tuberculosis.
Qinglan WangHelena I M BoshoffJustin R HarrisonPeter C RaySimon R GreenPaul G WyattClifton Earl BarryPublished in: Science (New York, N.Y.) (2020)
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.
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- cell wall
- mesenchymal stem cells
- cell cycle arrest
- cell death
- emergency department
- blood pressure
- blood glucose
- endothelial cells
- staphylococcus aureus
- cystic fibrosis
- insulin resistance
- skeletal muscle
- drug delivery
- biofilm formation
- amino acid
- bone regeneration
- hiv aids
- antiretroviral therapy
- electronic health record