title: Exploring prospects of novel drugs for tuberculosis.
abstract: Tuberculosis remains a disease with an enormous impact on public health worldwide. With the continuously increasing epidemic of drug-resistant tuberculosis, new drugs are desperately needed. However, even for the treatment of drug-sensitive tuberculosis, new drugs are required to shorten the treatment duration and thereby prevent development of drug resistance. Within the past ten years, major advances in tuberculosis drug research have been made, leading to a considerable number of antimycobacterial compounds which are now in the pipeline. Here we discuss a number of these novel promising tuberculosis drugs, as well as the discovery of two new potential drug targets for the development of novel effective drugs to curb the tuberculosis pandemic, ie, the coronin 1 and protein kinase G pathways. Protein kinase G is secreted by mycobacteria and is responsible for blocking lysosomal delivery within the macrophage. Coronin 1 is responsible for activating the phosphatase, calcineurin, and thereby preventing phagosome-lysosome fusion within the macrophage. Blocking these two pathways may lead to rapid killing of mycobacteria.
authors.affiliation: Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Janssen
authors.forename: Rajesh
authors.initials: R
authors.lastname: Jayachandran
authors.forename: Lulama
authors.initials: L
authors.lastname: Khathi
authors.forename: Jakob
authors.initials: J
authors.lastname: Zinsstag
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.forename: Jean
authors.initials: J
authors.lastname: Pieters
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D008840:Microfilament Proteins; C072061:coronin proteins; D017869:Cyclic GMP-Dependent Protein Kinases