Drug resistance mechanisms and novel drug targets for tuberculosis therapy

Drug-resistant tuberculosis （TB） poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug- resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuber- culosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

Post-exposure prophylaxis(PEP)for leprosy is administered as one single dose of rifampicin(SDR)to the contacts of newly diagnosed leprosy patients.SDR reduces the risk of developing leprosy among contacts by around 60%in the first 2–3 years after receiving SDR.In countries where SDR is currently being implemented under routine programme conditions in defined areas,questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M.tuberculosis strains circulating in these areas.This issue has not been addressed in scientific literature to date.To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis,a meeting was convened with tuberculosis(TB)and leprosy experts.The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of(multi)drug-resistance in M.tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy.They concluded that SDR given to contacts of leprosy patients,in the absence of symptoms of active TB,poses a negligible risk of generating resistance in M.tuberculosis in individuals and at the population level.Thus,the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M.tuberculosis.