Biochemical controls: expanding bacterial walls (Introduction)

by David Turell , Thursday, July 20, 2023, 17:43 (283 days ago) @ David Turell

Crack open and fill up:

https://phys.org/news/2023-07-achilles-heel-bacterial-cell-wall.html

"The bacterial cell wall must be constantly remodeled in order to grow and divide. This involves the close coordination of lytic enzymes and peptidoglycan synthesis. In their study published in Nature Communications, researchers led by Martin Thanbichler have now found that a central regulator can control completely different classes of autolysins.

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"Most bacterial species synthesize a semi-rigid cell wall surrounding the cytoplasmic membrane, whose main component, peptidoglycan, forms a dense meshwork that encases the cell. In addition to its protective role, the cell wall also serves as a means to generate specific cell shapes, such as spheres, rods, or spirals, thus facilitating motility, surface colonization, and pathogenicity.

"The presence of a cell wall presents its own challenges: cells must constantly remodel it in order to grow and divide. To do this, they must very carefully make tears in the wall to allow it to expand and change, while quickly mending the gaps with new material to prevent it from collapsing.

"This cell wall remodeling process involves the cleavage of bonds by lytic enzymes, also known as autolysins, and the subsequent insertion of new cell wall material by peptidoglycan synthases. The activities of these two antagonistic groups of proteins must be closely coordinated to prevent weak spots in the peptidoglycan layer that lead to cell lysis and death.

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"Analysis of potential autolysin regulators by co-immunoprecipitation screening and in vitro protein-protein interaction assays has revealed that a factor called DipM plays a pivotal role in bacterial cell wall remodeling. This key regulator, a soluble periplasmic protein, surprisingly interacts with several classes of autolysins as well as a cell division factor, showing a promiscuity that was previously unknown for this type of regulator.

"DipM was able to stimulate the activity of two peptidoglycan-cleaving enzymes with completely different activities and folding, making it the first identified regulator that can control two classes of autolysins. Notably, the results also indicate that DipM uses a single interface to interact with its various targets.

"'Disruption of DipM leads to the loss of regulation at various points of the cell wall remodeling and division process and ultimately kills the cell," says doctoral student Adrian Izquierdo Martinez, first author of the study. "Its proper function as a coordinator of autolysin activity is thus critical for proper cell shape maintenance and cell division in C. crescentus."

"The comprehensive characterization of DipM revealed a novel interaction network, including a self-reinforcing loop that connects lytic transglycosylases and possibly other autolysins to the core of the cell division apparatus of C. crescentus, and very likely also other bacteria. Thus, DipM coordinates a complex autolysin network whose topology greatly differs from that of previously studied autolysin systems.

"Martin Thanbichler points out, "The study of such multi-enzyme regulators, whose malfunction affects several cell wall-related processes at the same time, not only helps us to understand how the cell wall responds to changes in the cell or the environment. It can also contribute to the development of new therapeutic strategies that combat bacteria by disrupting several autolytic pathways simultaneously.' "

Comment: the earliest bacterial forms had to have had this mechanism to expand its cell wall and divide or the species would not have reproduced and survive. This degree of complexity is ancient and must have been designed when the first bacteria were formed.