In Vivo

All pathogens must acquire and assimilate nutrients from their hosts in order to grow and multiply -- our tissues are literally their food -- yet surprisingly little is known about this fundamental aspect of the pathogenic lifestyle. Accumulating evidence suggests that M. tuberculosis might utilize fatty acids as its principal carbon and energy source during infection. The fourth part of this lecture describes work in our laboratory that is focused on identifying the metabolic pathways that...

The principal obstacle to successful treatment of tuberculosis is the lengthy duration of current regimens, which require administration of multiple drugs for 6-9 months. The requirement for prolonged therapy is attributed to sub-populations of bacillary "persisters" that are refractory to antimicrobials. The persisters are not drug-resistant in the conventional (heritable) sense and it is a mystery why they are spared whilst their genetically identical siblings are killed. The third part of...

Tuberculosis remains one of the most important causes of human disease and death despite the introduction of vaccination in 1921 and chemotherapy in 1952. Although these interventions are inexpensive and widely available their impact is limited. The effectiveness of vaccination is unclear; in clinical trials, the protection conferred by vaccination has been variable and generally poor. Although chemotherapy can be highly effective, multiple drugs must be administered for 6-9 months to provide...

Human population growth and urbanization have accelerated dramatically in recent centuries, providing unprecedented opportunities for microbes that use our bodies as vehicles for their own propagation and transmission. These conditions have led to the emergence of virulent new pathogens and the increased prevalence of "classic" scourges, such as Mycobacterium tuberculosis. This tenacious microbe is transmitted via infectious aerosols produced by individuals with pulmonary tuberculosis....