The number of new tuberculosis (TB) cases is still rising and reached almost 10 million in 2010. This extraordinary impact on public health is in part due to drug-resistant M. tuberculosis strains, which have acquired resistance to four or more TB drugs. Such extensively drug-resistant (XDR) strains continue to emerge and spread, and are associated with particularly poor treatment outcomes. Success rates for treating XDR-TB are generally low and mortality can reach 100 percent for outbreaks in patients co-infected with HIV. New drugs are thus needed to limit the impact of TB on global health.
Significant progress has recently been made in the identification and characterization of new antimycobacterial compounds. However, the attrition rate in drug discovery is high and it is unlikely that the relatively small number of current lead compounds will solve the global health problems caused by (drug-resistant) TB. Target validation and the identification of new lead compounds, therefore, represent significant bottlenecks in TB drug development.
To overcome one of these obstacles we recently developed new genetic tools that allow us to conditionally inactivate M. tuberculosis genes in vitro and at different time points of an infection. We are currently applying these tools to study many genes of M. tuberculosisand aim to rank them according to their suitability for the development of new drugs against TB.