Modes of cell wall growth differentiation in rod-shaped bacteria
Introduction
Bacterial proliferation depends on the ability of each individual cell to periodically enlarge and divide in a way compatible with the regeneration of the initial shape and size in daughter cells. Conceptually the easiest way to achieve this goal is volume doubling followed by symmetric fission, as exemplified by many of the more commonly used model bacterial species (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Streptococcus pneumoniae, etc.). However, this is by no means the only possible way. Indeed, Caulobacter crescentus is a well-known example of a species in which division results in unequal offspring [1].
The cell wall (peptidoglycan layer, abbreviated PG, or murein sacculus) is a major element to consider for an appropriate understanding of bacterial growth. Because the sacculus is a covalently closed, stress-bearing, net-like giant molecule coating the cytoplasmic membrane, cell shape and growth are constrained by coordinated changes in the physical dimensions of the sacculus. Although the sacculus is elastic and can be considerably stretched [2], continuous cell growth, division, and generation of shape and cell appendages require incorporation of new precursors into the existing cell wall fabric. Incorporation by itself would not lead to expansion of the sacculus unless some of the existing bonds were cleaved concomitantly with the insertion of new PG subunits, a function performed by specialized PG modifying endopeptidase enzymes [3, 4]. Otherwise, sacculi would simply become thicker. Furthermore, in order to generate a precise shape, both incorporation and cleavage must take place at specific locations, rates, and times, that is, with a defined topology. Unfortunately, appropriate experimental tools to explore the delicate balance of cell wall removal and incorporation have been in short supply, and only very recently efficient methods to either label [5, 6••, 7, 8] or visualize growth sites [9••, 10••] have become available. Here we provide a survey of the state of research on cell wall growth topology and dynamics in rod-like bacteria. For the case of round and ovoid bacteria (Figure 1), the reader is referred to excellent recent reviews [11, 12].
Section snippets
Septal PG synthesis
Not surprisingly, research on E. coli has remained at the forefront of the bacterial cell wall biosynthesis field. The topology of PG synthesis in this species was first addressed 40 years ago in the pioneering work of Ryter et al. [13] using radioactive PG precursors and autoradiography. Further refinement of the methodology combined with the mathematical modeling of the data by Verwer and Nanninga led to the proposal of a dispersed mode of cell wall growth with a higher probability of
Cell elongation by dispersed PG synthesis
In E. coli and other species like B. subtilis, growth in length is not predominantly dependent on the zonal system, but rather on the dispersed incorporation of precursors at discrete sites over the cylindrical cell body (Figure 1). As is the case for septal PG synthesis, the elongation PG biosynthetic complexes are made of a large number of molecules [27]. Biosynthetic complexes include not only the polymerizing machinery (PBPs and ancillary proteins) but also (some) precursor-synthesizing
Cell elongation by zonal growth
Not all rod-shaped bacteria elongate by dispersed incorporation of precursors; indeed many do so by zonal incorporation. In such a situation, both elongation and division occur at the same cellular location, but not at the same time. Newborn cells differentiate a zonal growth site which first promotes cell elongation and then is modified to promote inwards growth of a septum (see review [43]). Division is coupled to inactivation of cell elongation PG synthesis at the new poles, and a new cycle
Conclusion
In the previous sections we described how current research is revealing the diversity of mechanisms underlying bacterial cell wall growth. As is often the case, the abundance of information on a few species is largely out-weighed by the restricted diversity of subjects. Nevertheless, it is quite evident that bacteria have found diverse ways to coordinate longitudinal growth with transverse division ensuring conservation of shape. The recently developed methodologies to visualize new PG in vivo,
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
Research in the Cava lab is supported by The Laboratory for Molecular Infection Medicine Sweden (MIMS) and by the Knut and Alice Wallenberg Foundation (KAW). Y.V.B. was supported by Grant GM51986 from the National Institutes of Health.
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