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

Qinglan Wang; Helena I. M. Boshoff; Justin R. Harrison; Peter C. Ray; Simon R. Green; Paul G. Wyatt; Clifton E. Barry

doi:10.1126/science.aav5912

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

Qinglan Wang, Helena I. M. Boshoff, Justin R. Harrison, Peter C. Ray, Simon R. Green, Paul G. Wyatt, Clifton E. Barry (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1147-1151
Number of pages	5
Journal	Science
Volume	367
Issue number	6482
DOIs	https://doi.org/10.1126/science.aav5912
Publication status	Published - 6 Mar 2020

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@article{efc57622d42f4a468911ab3888e0ec94,

title = "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.",

author = "Qinglan Wang and Boshoff, {Helena I. M.} and Harrison, {Justin R.} and Ray, {Peter C.} and Green, {Simon R.} and Wyatt, {Paul G.} and Barry, {Clifton E.}",

note = "Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

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TY - JOUR

T1 - PE/PPE proteins mediate nutrient transport across the outer membrane of Mycobacterium tuberculosis

AU - Wang, Qinglan

AU - Boshoff, Helena I. M.

AU - Harrison, Justin R.

AU - Ray, Peter C.

AU - Green, Simon R.

AU - Wyatt, Paul G.

AU - Barry, Clifton E.

PY - 2020/3/6

Y1 - 2020/3/6

N2 - 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.

AB - 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.

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DO - 10.1126/science.aav5912

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C2 - 32139546

SN - 0036-8075

VL - 367

SP - 1147

EP - 1151

JO - Science

JF - Science

IS - 6482

ER -

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

Abstract

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