Robust peptidoglycan growth by dynamic and variable multi-protein complexes

Abstract

In Gram-negative bacteria such as Escherichia coli the peptidoglycan sacculus resides in the periplasm, a compartment that experiences changes in pH value, osmolality, ion strength and other parameters depending on the cell's environment. Hence, the cell needs robust peptidoglycan growth mechanisms to grow and divide under different conditions. Here we propose a model according to which the cell achieves robust peptidoglycan growth by employing dynamic multi-protein complexes, which assemble with variable composition from freely diffusing sets of peptidoglycan synthases, hydrolases and their regulators, whereby the composition of the active complexes depends on the cell cycle state - cell elongation or division - and the periplasmic growth conditions.

Lytic transglycosylases: concinnity in concision of the bacterial cell wall

“…Bacteria preserve the integrity of their cell envelope during growth and cell division by the integration of an array of interwoven pathways (Pazos et al , 2017). A key component of this envelope and focus of these pathways is a peptidoglycan polymer—the cell wall—that fully surrounds the bacterium.…”

Peptidoglycan in obligate intracellular bacteria

“…Chemical modifications are found in the glycan backbone or peptides, and these may have emerged in response to selective pressure on peptidoglycan from peptidoglycan-targeting enzymes or antibiotics (Vollmer and Tomasz, 2002;Vollmer, 2008;Figueiredo et al, 2012). Given the importance of a structurally intact sacculus on bacterial cell integrity, the polymerisation and insertion of new peptidoglycan strands is a complex and robustly regulated process (Typas et al, 2012;Pazos et al, 2017) and this is particularly critical in the context of bacterial cell division (Egan and Vollmer, 2013).…”

Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

“…A second level of uncertainty refers to regulators, acting at the transcriptional or post‐transcriptional level, that control expression and activity of PG enzymes and for which we are still at a very early stage of knowledge. Some exceptions include: (a) the essential transmembrane protein kinases bearing PASTA (penicillin‐binding protein and serine/threonine kinase associated) domains that control PG synthesis and cell wall homeostasis in low G + C Gram‐positive bacteria (Dubrac, Bisicchia, Devine, & Msadek, ; Jones & Dyson, ); (b) the sigma‐type regulators that regulate expression of PG enzymes driving the synthesis of an unique PG during spore formation and germination in the mother cell, the forespore and the mature spore (Popham & Bernhards, ); and, (c) proteins that associate in complexes with synthases and hydrolases regulating their activity by protein‐protein interactions (Egan, Cleverley, Peters, Lewis, & Vollmer, ; Pazos, Peters, & Vollmer, ). Intriguingly, most PG enzymes controlled by these regulators are periplasmic synthases and hydrolases, reinforcing the idea of macromolecular PG as a sensor device that integrates external signals upon exposure to stress.…”

“…This is especially relevant for enzymes predicted to act in identical bonds of the PG sacculus -the repeatedly discussed redundancy-or for those enzymes with multiple paralogs of yet unknown function. The global analysis performed 'at the protein level' will be, in my opinion, insightful to understand why these apparent multiple copies exist and if compensatory effects formation and germination in the mother cell, the forespore and the mature spore (Popham & Bernhards, 2015); and, (c) proteins that associate in complexes with synthases and hydrolases regulating their activity by protein-protein interactions (Egan, Cleverley, Peters, Lewis, & Vollmer, 2017;Pazos, Peters, & Vollmer, 2017). Intriguingly, most PG enzymes controlled by these regulators are periplasmic synthases and hydrolases, reinforcing the idea of macromolecular PG as a sensor device that integrates external signals upon exposure to stress.…”