Thioridazine Alters the Cell-Envelope Permeability of Mycobacterium tuberculosis.
J Proteome Res
; 15(6): 1776-86, 2016 06 03.
Article
in En
| MEDLINE
| ID: mdl-27068340
ABSTRACT
The increasing occurrence of multidrug resistant tuberculosis exerts a major burden on treatment of this infectious disease. Thioridazine, previously used as a neuroleptic, is active against extensively drug resistant tuberculosis when added to other second- and third-line antibiotics. By quantitatively studying the proteome of thioridazine-treated Mycobacterium tuberculosis, we discovered the differential abundance of several proteins that are involved in the maintenance of the cell-envelope permeability barrier. By assessing the accumulation of fluorescent dyes in mycobacterial cells over time, we demonstrate that long-term drug exposure of M. tuberculosis indeed increased the cell-envelope permeability. The results of the current study demonstrate that thioridazine induced an increase in cell-envelope permeability and thereby the enhanced uptake of compounds. These results serve as a novel explanation to the previously reported synergistic effects between thioridazine and other antituberculosis drugs. This new insight in the working mechanism of this antituberculosis compound could open novel perspectives of future drug-administration regimens in combinational therapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thioridazine
/
Cell Membrane Permeability
/
Proteome
/
Mycobacterium tuberculosis
Language:
En
Journal:
J Proteome Res
Journal subject:
BIOQUIMICA
Year:
2016
Document type:
Article