Ultrastructure of mycobacterial surfaces by freeze-substitution

The global status of tuberculosis has recently received much public attention, particularly in some developed countries that are now reporting an increase in cases after several years of decline. A number of factors have contributed to the resurgence in tuberculosis and other mycobacterial infections, including homelessness, increased urban overcrowding among the poor, increased drug abuse and the AIDS epidemic. In addition, the intrinsic nature of mycobacterial impermeability to some antibiotics, and their ability to survive in host environments has been attributed to the unique chemistry and architecture of their walls. A better understanding of these surface-related properties could in turn lead to the design of more effective chemotherapeutic agents or potential vaccine candidates. Using freeze-substitution, we offer a revised perspective on mycobacterial wall design and discuss its significance.