Free Content Targeting human macrophages for enhanced killing of intracellular XDR-TB and MDR-TB [Review article]

Authors: Martins, M.1; Viveiros, M.2; Couto, I.3; Amaral, L.1

Source: The International Journal of Tuberculosis and Lung Disease, Volume 13, Number 5, May 2009 , pp. 569-573(5)

Publisher: International Union Against Tuberculosis and Lung Disease

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Abstract:

Although many compounds have been described to inhibit the replication of drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis, most of these studies only evaluate their in vitro activity. There is a lack of studies that show whether any of these agents can kill these organisms at the site where they normally reside post infection, namely, the macrophage of the lung parenchyma.

It is the aim of this mini-review to identify agents that have been shown to enhance the killing of intracellular drug-susceptible, multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains by non-killing macrophages. Because these agents appear to promote their activity by affecting the transport of K+ and Ca2+ from the phagolysosome containing the bacteria, and thereby promoting its acidification and activation of hydrolases that will eventually kill the organism, the authors suggest that compounds that are known to affect the transport of K+ and Ca2+ should be considered for possible activity against intracellular MDR- and XDR-TB.

Keywords: MDR-TB; XDR-TB; macrophage activation; enhancement of killing activity; K+ and Ca2+ inhibition

Document Type: Review article

Affiliations: 1: Unit of Mycobacteriology and Unidade de Parasitologia e Microbiologia Médicas (UPMM), Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL), Lisboa, Portugal 2: Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL), Lisboa, Portugal 3: Unit of Mycobacteriology, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL), Lisboa, Portugal; and Centro de Recursos Microbiológicos (CREM), Faculdade de Ciências e Tecnologia, Caparica, Portugal

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