Explaining how slow-growing tuberculosis bacteria acquire nutrients across their membranes, without also becoming vulnerable to drugs that target them, researchers report a crucial role in this for a family of porin-like proteins in the bacteria's notoriously tough, waxy coating. The results provide valuable new insights that could be leveraged in the development of novel tuberculosis drugs.
Mycobacterium tuberculosis infections - the cause of tuberculosis - are notoriously difficult to treat. The pathogen can be highly resistant to both antibiotic treatments and to the relentless attacks mobilized by the host's immune system.
Like other slow-growing mycobacteria, M. tuberculosis are clad in a unique, wax-like outer membrane, which allows the pathogen to persist in the hostile conditions in the human body. Though this armored coating is nigh impenetrable to most small molecules, essential nutrients are still able to slip past the cell's waxy defenses.
How this happens, however, remains enigmatic, but manipulation of channels involved - once identified - could provide a way to enhance the pathogen's susceptibility to antibiotics. While evaluating a simple molecule particularly effective at killing M. tuberculosis, the authors discovered a unique role of PE/PPE proteins, a large family of abundant mycobacteria-specific proteins associated with the outer envelope of the pathogen and its virulence. PE/PPE proteins have long been considered vital to M. tuberculosis virulence, though their function has been enigmatic.
The authors 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. The authors conclude that several PE/PEE proteins act as pore-like protein, or porins, that ferry vital nutrients across the cell's waxy wall, allowing M. tuberculosis to survive and spread while under antibiotic siege.
https://science.sciencemag.org/content/367/6482/1147
How nutrients across Mycobacterium tuberculosis defensive walls transported
- 1,269 views
- Added
Edited
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
Gene to regulate sleep!
Read more
Why do we still have mitochondrial DNA?
Read more
New mathematical model to explain human genome mutation variability
Read more
Mutation in bile acid receptor identified!
Read more
A gene associated with a set of poorly understood rare diseases ide…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar