Targeting human macrophages for enhanced killing of intracellular XDR-TB and MDR-TB.
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 Ca(2+) 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 Ca(2+) should be considered for possible activity against intracellular MDR- and XDR-TB.
Martins
M
M
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.
Viveiros
M
M
Couto
I
I
Amaral
L
L
D000995:Antitubercular Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology
D000995:Antitubercular Agents