Bacterial growth and cell division: a mycobacterial perspective

Abstract

The genus Mycobacterium is best known for its two major pathogenic species, M. tuberculosis and M. leprae, the causative agents of two of the world's oldest diseases, tuberculosis and leprosy, respectively. M. tuberculosis kills approximately two million people each year and is thought to latently infect one-third of the world's population. One of the most remarkable features of the nonsporulating M. tuberculosis is its ability to remain dormant within an individual for decades before reactivating into active tuberculosis. Thus, control of cell division is a critical part of the disease. The mycobacterial cell wall has unique characteristics and is impermeable to a number of compounds, a feature in part responsible for inherent resistance to numerous drugs. The complexity of the cell wall represents a challenge to the organism, requiring specialized mechanisms to allow cell division to occur. Besides these mycobacterial specializations, all bacteria face some common challenges when they divide. First, they must maintain their normal architecture during and after cell division. In the case of mycobacteria, that means synthesizing the many layers of complex cell wall and maintaining their rod shape. Second, they need to coordinate synthesis and breakdown of cell wall components to maintain integrity throughout division. Finally, they need to regulate cell division in response to environmental stimuli. Here we discuss these challenges and the mechanisms that mycobacteria employ to meet them. Because these organisms are difficult to study, in many cases we extrapolate from information known for gram-negative bacteria or more closely related GC-rich gram-positive organisms.

FIG. 1.

Diagram of the basic components of the mycobacterial cell wall. MAPc, MA-AG-PG complex.

FIG. 2.

Synthesis of PG. Major steps are shown, with precursors such as UDP-NAM, lipid I, and lipid II being synthesized within the cytoplasm. Lipid II is then transported across the lipid membrane, and periplasmic transglycosylases and endopeptidases link the PG monomer into existing PG sheets through β-1,4 glycosidic linkages and DAP-DAP peptide cross-linkages.

FIG. 3.

Localization of nascent and inert PG in different bacteria.

FIG. 4.

V-snapping process of mycobacteria during cell division.

FIG. 5.

Cycle of mycobacteria entering and exiting dormancy. Environmental conditions and proteins thought to be involved with inducing transitions between the two life cycle stages are listed.