Bacterial Growth and Cell Division: a Mycobacterial Perspective

Abstract

SUMMARY 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.

Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria

“…In either scenario, the mechanism responsible for division-site selection is unknown. Although proteins equivalent to the well-characterized minicell and nucleoid occlusion systems are apparently absent in mycobacteria 33 , new factors such as the chromosomepartitioning protein ParA have been postulated to have a role in septum positioning 34 . In future experiments, it will be informative to employ reporter strains expressing multiple fluorescently tagged division proteins in order to determine the relative timing of appearance of these markers at the future site of cell division.…”

Characterization of CrgA, a New Partner of the Mycobacterium tuberculosis Peptidoglycan Polymerization Complexes

“…Mycobacteria lack identifiable homologs for MreB (30). We propose that in the absence of MreB and owing to its interactions with FtsZ, FtsQ, and FtsI, CrgA may facilitate the recruitment of the peptidoglycan synthesis machinery to poles and septal zones and possibly coordinate peptidoglycan synthesis at these sites.…”

“…Although cell division machinery is generally well conserved in eubacteria, mycobacteria lack genes encoding several wellcharacterized regulatory proteins, e.g., EzrA, ZapA, ZapB, SulA, and MinCDE, and also some integral components, e.g., FtsA, FtsN, and FtsB (30). Despite this fact, the slow polymerization and weak GTP hydrolysis activities of M. tuberculosis FtsZ combined with the presence of novel proteins such as ChiZ and FipA, which indirectly or directly modulate FtsZ ring assembly, impart uniqueness to the mycobacterial cell division machinery (6,7,45,52).…”

Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus

“…Mycobacteria are structurally Gram-positive bacteria, because they have a poor true outer membrane that contains a thick peptidoglycan layer. However, they also share properties with Gram-negative organisms, as they do not retain Gram staining (30). Therefore, it is unknown whether the novel oxazolidinone LCB01-0371 can be applied to mycobacterial infections.…”