The Dream of a Mycobacterium

Abstract

How do mycobacteria divide? Cell division has been studied extensively in the model rod-shaped bacteria Escherichia coli and Bacillus subtilis, but much less is understood about cell division in mycobacteria, a genus that includes the major human pathogens M. tuberculosis and M. leprae. In general, bacterial cell division requires the concerted effort of many proteins in both space and time to elongate the cell, replicate and segregate the chromosome, and construct and destruct the septum - processes which result in the creation of two new daughter cells. Here, we describe these distinct stages of cell division in B. subtilis and follow with the current knowledge in mycobacteria. As will become apparent, there are many differences between mycobacteria and B. subtilis in terms of both the broad outline of cell division and the molecular details. So, while the fundamental challenge of spatially and temporally organizing cell division is shared between these rod-shaped bacteria, they have solved these challenges in often vastly different ways.

FIGURE 1

Characteristics of growth and division in B. subtilis and mycobacteria. B. subtilis and E. coli grow by adding new cell wall (gray) along the lateral cell body. Mycobacteria grow only at the polar regions, and do so at unequal amounts depending on the identity of the pole. This is observed by using a cell wall dye (green) to stain the existing cell wall and observe outgrowth of the newly synthesized, unstained cell wall (7). Arrows, polar location of new cell wall synthesis (a large arrow indicates more growth); dotted line, septum; green portion, old cell wall; gray portion, new cell wall.

FIGURE 2

Polar growth segregates the cell wall based on age. (Top) Fluorescent d-amino acids are thought to incorporate into nascent PG. Pulse chase with these shows how the new and old cell walls are spatially segregated in M. smegmatis (Baranowski C, Rego EH, and Rubin EJ, unpublished images). (Bottom) Alexa-488 NHS ester stains the existing cell wall (green). New cell wall is unstained and can be monitored using time-lapse microscopy. After two divisions, the oldest cell wall is inherited by the new pole daughter cells (*) in M. smegmatis. (Baranowski, Rego, and Rubin. unpublished images; 7).

FIGURE 3

Mycobacterial divisome interactions. A schematic of mycobacterial divisome protein interactions. Note that interactions are not necessarily direct given the available data. Gray dotted lines, physical interactions; red dotted lines, negative regulation; brown lines, FtsQ pulldown proteins (44); blue text, cell wall enzymes; orange text, kinases.

FIGURE 4

Mycobacterial divisome and elongasome members. (Top) Schematic of proteins involved in mycobacterial cell division. Proteins marked with an asterisk (*) have been shown to interact with FtsZ. The FtsZ ring is illustrated as a dark gray circle upon which the divisome members are arranged. (Bottom) Schematic of proteins involved in mycobacterial elongation. Interacting proteins are depicted touching, and proteins with a question mark (?) may belong in these complexes, but data are limited.