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

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.

• Authors: Leonard Amaral, Ana Martins, Joseph Molnar, Jette E Kristiansen, Marta Martins, Miguel Viveiros, Liliana Rodrigues, Gabriella Spengler, Isabel Couto, Jorge Ramos, Sujata Dastidar, Séamus Fanning, Matt McCusker, Jean-Marie Pages
• Journal: In vivo (Athens, Greece) (In Vivo) 2010 Jul-Aug Vol. 24 Issue 4 Pg. 409-24 ISSN: 0258-851X [Print] Greece
• PMID: 20668307 (Publication Type: Journal Article)

Chemical References

• Antipsychotic Agents
• Antitubercular Agents
• Phenothiazines
• Chlorpromazine

Topics

• Animals
• Antipsychotic Agents (therapeutic use)
• Antitubercular Agents (pharmacology, therapeutic use)
• Chlorpromazine (therapeutic use)
• Drug Resistance, Multiple
• Humans
• Macrophages (drug effects, physiology)
• Mycobacterium tuberculosis (drug effects)
• Phenothiazines (pharmacology, therapeutic use)
• Salmonella Infections (drug therapy)
• Salmonella typhimurium (drug effects)
• Staphylococcal Infections (drug therapy)
• Staphylococcus aureus (drug effects)
• Tuberculosis (drug therapy, microbiology)