The global status of tuberculosis has recently received much public at
tention, particularly in some developed countries that are now reporti
ng an increase in cases after several years of decline. A number of fa
ctors have contributed to the resurgence in tuberculosis and other myc
obacterial infections, including homelessness, increased urban overcro
wding among the poor, increased drug abuse and the AIDS epidemic. In a
ddition, the intrinsic nature of mycobacterial impermeability to some
antibiotics, and their ability to survive in host environments has bee
n attributed to the unique chemistry and architecture of their walls.
A better understanding of these surface-related properties could in tu
rn lead to the design of more effective chemotherapeutic agents or pot
ential vaccine candidates. Using freeze-substitution, we offer a revis
ed perspective on mycobacterial wall design and discuss its significan
ce.