Is the mycobacterial cell wall a hopeless drug target for latent tuberculosis?

The cell wall of Mycobacterium tuberculosis has an ambivalent reputation as a drug target because front-line agents such as isoniazid target core cell wall processes, yet nonreplicating cells do not synthesize new cell wall. In this review we consider the evidence from a variety of bacterial species that cell wall structure is not static but is a dynamic polymer that adapts to growth-phase and the environmental conditions in which the organisms reside. Intermittent phases of nonreplication thus are likely to be attended by specific cell wall structural alterations that are highly valuable for targeting by new chemotherapeutics. There is a paucity of information about the details and physiological importance of these structural adaptations; thus, the identity of the most vulnerable cell wall drug targets remains elusive.

Section editors:William Bishai – Johns Hopkins School of Medicine, Baltimore, MD, USAEric Nuermberger – Johns Hopkins School of Medicine, Baltimore, MD, USA