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Home / Publicações / Clinical relevance of multiple single-nucleotide polymorphisms in Pneumocystis jirovecii pneumonia: development of a multiplex PCR-single-base-extension.

Clinical relevance of multiple single-nucleotide polymorphisms in Pneumocystis jirovecii pneumonia: development of a multiplex PCR-single-base-extension.

  • Autores: Amaral L, Dastidar SG, Dutta NK, Karakousis PC, Mazumdar K
  • Journal: Recent Patents on Anti-Infective Drug Discovery
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=New+patentable+use+of+an+old+neuroleptic+compound+thioridazine+to+combat+tuberculosis%3A+a+gene+regulation+perspective

Use of the old antipsychotic phenothiazine thioridazine (THZ) for therapy of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) infection is now being seriously considered. It is reported that THZ primarily acts on enzymes involved in fatty acid metabolism and membrane proteins, particularly efflux pumps, as well as oxidoreductases and proteins involved in aerobic respiration that overlap with a number of conventional antituberculous drugs. It targets the products of the Rv3160c-Rv3161c operon, which are perhaps required for the detoxification of THZ, members of the sigma factor SigB regulon that play a crucial role in protecting the pathogen against cell envelope damage, and Rv2745c, a transcription factor that regulates ATP-dependent proteolysis. Some of these genes have been shown to be essential for the survival or persistence of Mycobacterium tuberculosis in the infected host. Since THZ targets multiple pathways, including those involved in cell wall processes and respiratory chain components, it may serve as a model for multi-target drug development, as well as constitute a highly potent addition to a combination of antituberculous drug regimens. The discussion of some of the patents relevant to thioridazine to combat tuberculosis is also included in the present manuscript.

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About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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