Prospects for the Development of New Antituberculous Drugs Based on the Drug Targets Related to Virulence Factors Interfering with Host Cytokine Networks

Abstract

Worldwide, tuberculosis remains the most frequent and important infectious disease to cause morbidity and death. However, the development of new drugs for the treatment and prophylaxis of TB has been slow. Therefore, novel types of antituberculous drugs, which act on the unique drug targets in Mycobacterium tuberculosis, particularly the drug targts related to the establishment of mycobacterial dormancy and persistency in host macrophages, are urgently needed. In this context, it should be noted that current antituberculous drugs mostly target the metabolic reactions and proteins which are essential for the growth of M. tuberculosis in extracellular milieus. It may also be promising to develop another type of drug that exhibits an inhibitory action against bacterial virulence factors which cross-talk and interfere with signaling pathways of M. tuberculosis-infected host immunocompetent cells such as macrophages and T cells, thereby changing the intracelluar milieus favorable to intramacrophage survival and growth of infected bacilli. In this review article, I will describe recent approaches to identify and establish novel potential drug targets in M. tuberculosis, especially those related to mycobacterial virulence factors interfering with host cytokine networks, particularly those acting upon intracellular signaling pathways of macrophages.