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.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
de Keijzer J,Mulder A,de Haas PE,de Ru AH,Heerkens EM,Amaral L,van Soolingen D,van Veelen PAdoi
10.1021/acs.jproteome.5b01037subject
Has Abstractpub_date
2016-06-03 00:00:00pages
1776-86issue
6eissn
1535-3893issn
1535-3907journal_volume
15pub_type
杂志文章abstract：:The skin is the primary boundary between the body and the environment. In addition to its properties as a physical barrier, skin keratinocytes actively participate in many defense mechanisms. Viral double-stranded RNA (dsRNA) is the most important viral structure involved in activation of immune response. Intracellula...
journal_title：Journal of proteome research
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