title: 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.affiliation: Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 96, 1349-008 Lisbon, Portugal. lamaral@ihmt.unl.pt
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
authors.forename: Ana
authors.initials: A
authors.lastname: Martins
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnar
authors.forename: Jette E
authors.initials: JE
authors.lastname: Kristiansen
authors.forename: Marta
authors.initials: M
authors.lastname: Martins
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Liliana
authors.initials: L
authors.lastname: Rodrigues
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Isabel
authors.initials: I
authors.lastname: Couto
authors.forename: Jorge
authors.initials: J
authors.lastname: Ramos
authors.forename: Sujata
authors.initials: S
authors.lastname: Dastidar
authors.forename: Séamus
authors.initials: S
authors.lastname: Fanning
authors.forename: Matt
authors.initials: M
authors.lastname: McCusker
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pages
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002746:Chlorpromazine / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010640:Phenothiazines / Q000494:pharmacology / Q000627:therapeutic use*; D012480:Salmonella Infections / Q000188:drug therapy; D012486:Salmonella typhimurium / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D014150:Antipsychotic Agents; D000995:Antitubercular Agents; D010640:Phenothiazines; D002746:Chlorpromazine