Back to the future: a new ‘old’ lead for tuberculosis

See related article in EMBO Molecular Medicine http://dx.doi.org/10.1002/emmm.201201689 ‘The Great White Plague, which only 10 years ago was thought to be immune to drug therapy, is gradually being eliminated. . . Streptomycin pointed a way. Later supplemented with PAS (para‐amino salicylic acid) and more recently with isoniazid, it has brought the control of this disease within sight’. Selman A. Waksman, Noble Prize Banquet Speech 1952. Despite the breakthroughs in management of tuberculosis noted by Waksman 8 years after his discovery of the first effective antitubercular drug, streptomycin (Schatz et al, 1944), the disease continues to infect, incapacitate and kill in the 21st century. Over 8.8 million are infected and 1.4 million die every year (www.who.int/mediacentre/factsheets/fs104/en/index.html). The organism that causes tuberculosis, Mycobacterium tuberculosis , has proven to be a formidable match for our ability to control disease. At the core of this challenge is the remarkable physiology and biochemistry of M. tuberculosis and its ability to reside in a dormant state within human macrophages. These unique characteristics necessitate multidrug therapy, typically ≥4 antibiotics, and extended periods of dosing (6–12 months). The rise of strains resistant to multiple drugs MDR (multi‐drug‐resistant) resistant to rifampin and isoniazid, XDR (extensive‐drug‐resistant) resistant to even more antibiotics, and now some strains totally impervious to all available drugs, TDR (totally drug‐resistant) raises the specter of the emergence of a global health care disaster and a return to a pre‐Waksman era of tuberculosis treatment (Zumla et al, 2012). The result is a great need for new therapies and a renewed effort to find new anti‐TB antibiotics. The result is a great need for new therapies …