Editorial [Tuberculosis Drugs and Drug Targets]

More than one-third of the global population is infected with the tuberculosis (TB) and TB remains one of the world’s leading causes of disease and death. Each year, 8 million people become ill with TB and 2 million people die from the disease. In addition, drug resistance in the form of MDR-TB (strains resistant to isoniazid and rifampicin) and XDR-TB (strains resistant to isoniazid and rifampicin, and to a fluoroquinolone and one of the injectable TB drugs [kanamycin, amikacin or capreomycin]) is making it more difficult to deliver effective therapy leading to a cure. Although drug discovery for new antitubercular agents diminished for many years, resurgence took place over the last several years with support from governments, research institutes, and non-profit foundations. Today there is active research in identifying new targets for drug discovery, validating new targets, and discovering new lead compounds for drug development. Although there are four new agents undergoing clinical trials, most are in the early stages and the final outcome is not yet known. Thus, efforts need to continue, especially efforts to discover new agents that can dramatically shorten the time needed in therapy. This special topics issue of Infectious Disorders - Drug Targets focuses on TB drugs, drug development and drug targets. The Evolution of Extensively Drug Resistant Tuberculosis (XDR-TB): History, Status and Issues for Global Control (Goldman, Plumley and Laughon): The selection and spread of multiple drug resistant M. tuberculosis continued for decades leading to selection and spread of two operationally distinct forms, multiple drug resistant (MDR-TB) and extensively drug resistant (XDR-TB). The estimate for MDR-TB and XDR-TB cases globally for 2005 were 424,000 and 27,000 respectively, and the situation is worst in areas with high incidences of HIV infection. This situation was brought to the forefront when an outbreak of XDR-TB occurred in Tugela Ferry, KwaZulu-Natal, South Africa, in 2005 and began to spread. The evolution of XDR-TB is reviewed in terms of its causes, commentary from the research and lay communities, and future health care needs to contain the global epidemic. Programs to Facilitate Tuberculosis Drug Discovery: The Tuberculosis Antimicrobial Acquisition and Coordinating Facility (Goldman, Laughon, Reynolds, Secrist III, Maddry, Poffenberger, Kwong, and Subramaniam): The Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) was founded to make comprehensive testing services available at no cost to research laboratories with an interest in discovering new TB drugs. The TAACF is managed and funded by the National Institute of Allergy and Infectious Diseases (National Institutes of Health, Bethesda, MD) as a resource to support preclinical drug discovery and development and consists of a series of government contracts supporting compound acquisition and storage, in vitro evaluation of antimycobacterial activity and cytotoxicity, development of high throughput assays, in vivo evaluation of toxicity, oral bioavailability and efficacy in animal models, specialty testing (such as activity against non-replicating persistent bacteria), and a component to assist in technology transfer for developing comprehensive promotional packages and facilitating partnerships with pharmaceutical companies for drug development. Challenges Associated with Current and Future TB Treatment (Laurenzi, Ginsberg and Spigelman): The current and future status of TB drugs is reviewed in the context of the emergence of drug resistance and the high incidence of TB-HIV co-infection. The difficulties in optimizing the use of existing drugs and challenges for development of novel, improved products for effectively treating TB are discussed. Molecular Approaches to Target Discovery: Evaluating Targets for Antituberculosis Drug Discovery Programmes (Balganesh and Furr): Issues related to the selection of valid targets for drug discovery are reviewed, including the issue of host targeting non-replicating, persistent bacteria. Factors for use in prioritizing targets are discussed along with the use of genomic information.......