Phenothiazines, bacterial efflux pumps and targeting the macrophage for enhanced killing of intracellular XDRTB

Leonard Amaral, Ana Martins, Joseph Molnár, Jette E. Kristiansen, Marta Martins, M Viveiros, L Rodrigues, Gabriella Spengler, I Couto, Jorge Ramos, Sujata Dastidar, Séamus Fanning, Matthew McCusker, Jean Marie Pagès

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Phenothiazines have their primary effects on the plasma membrane of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources, energy providing enzymes such as ATPases, and genes that regulate and code for permeability aspects of the bacterium. The responses of multi-drug (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis to the neuroleptic phenothiazine thioridazine are reviewed. The information collated suggests that this phenothiazine has the potential to cure XDR and MDR tuberculosis infections, a potential that has been recently demonstrated by its ability to cure 10 patients who presented with XDR TB infections. The mechanism by which this phenothiazine produces the desired effects within the infected macrophage is also discussed.
Original languageEnglish
Pages (from-to)409-424
Number of pages16
JournalIn Vivo
Volume24
Issue number4
Publication statusPublished - Jun 2010

Keywords

  • Phenothiazines
  • Thioridazine
  • Pulmonary tuberculosis
  • MDR TB
  • XDR TB
  • Human macrophage
  • Enhanced killing activity by macrophage
  • Efflux pumps
  • Therapy with thioridazine
  • Review

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

Fingerprint Dive into the research topics of 'Phenothiazines, bacterial efflux pumps and targeting the macrophage for enhanced killing of intracellular XDRTB'. Together they form a unique fingerprint.

Cite this