Phenothiazines, bacterial efflux pumps and targeting the macrophage for enhanced killing of intracellular XDRTB.
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.
Amaral
Leonard
L
Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua Junqueira 96, 1349-008 Lisbon, Portugal. lamaral@ihmt.unl.pt
Martins
Ana
A
Molnar
Joseph
J
Kristiansen
Jette E
JE
Martins
Marta
M
Viveiros
Miguel
M
Rodrigues
Liliana
L
Spengler
Gabriella
G
Couto
Isabel
I
Ramos
Jorge
J
Dastidar
Sujata
S
Fanning
Séamus
S
McCusker
Matt
M
Pages
Jean-Marie
JM
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
D014150:Antipsychotic Agents; D000995:Antitubercular Agents; D010640:Phenothiazines; D002746:Chlorpromazine