Don’t let sleeping dogmas lie: new views of peptidoglycan synthesis and its regulation

Zhao, Heng; Patel, Vaidehi; Helmann, John D.; Dörr, Tobias

doi:10.1111/mmi.13853

Cited by 90 publications

(108 citation statements)

References 122 publications

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“…The cell wall is a crucial structural feature for the vast majority of bacteria and is mainly composed of a rigid, yet elastic, covalently‐bound network of peptidoglycan (PG) strands. PG has an oligomeric glycan backbone that is assembled by glycosyltransferases (GTs, RodA/FtsW and class A Penicillin Binding Proteins [aPBPs]) (Cho et al , ; Leclercq et al , ; Zhao et al , ; Taguchi et al , ) through the polymerization of N ‐acetylglucosamine (NAG)‐ N ‐acetylmuramic acid (NAM) heterodimers. These PG strands are crosslinked to adjacent strands primarily by the transpeptidase domains of aPBPs and bPBPs via short peptides attached to the NAM residues, resulting in the strong, mesh‐like sacculus.…”

Section: Introductionmentioning

confidence: 99%

Lytic transglycosylases RlpA and MltC assist in Vibrio cholerae daughter cell separation

Weaver

Jiménez-Ruiz

Tallavajhala

et al. 2019

Molecular Microbiology

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Summary The cell wall is a crucial structural feature in the vast majority of bacteria and comprises a covalently closed network of peptidoglycan (PG) strands. While PG synthesis is important for survival under many conditions, the cell wall is also a dynamic structure, undergoing degradation and remodeling by ‘autolysins’, enzymes that break down PG. Cell division, for example, requires extensive PG remodeling, especially during separation of daughter cells, which depends heavily upon the activity of amidases. However, in Vibrio cholerae, we demonstrate that amidase activity alone is insufficient for daughter cell separation and that lytic transglycosylases RlpA and MltC both contribute to this process. MltC and RlpA both localize to the septum and are functionally redundant under normal laboratory conditions; however, only RlpA can support normal cell separation in low‐salt media. The division‐specific activity of lytic transglycosylases has implications for the local structure of septal PG, suggesting that there may be glycan bridges between daughter cells that cannot be resolved by amidases. We propose that lytic transglycosylases at the septum cleave PG strands that are crosslinked beyond the reach of the highly regulated activity of the amidase and clear PG debris that may block the completion of outer membrane invagination.

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Section: Introductionmentioning

confidence: 99%

Lytic transglycosylases RlpA and MltC assist in Vibrio cholerae daughter cell separation

Weaver

Jiménez-Ruiz

Tallavajhala

et al. 2019

Molecular Microbiology

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“…The rotation of MreB in the cytoplasm is coupled with synthesis of PG occurred in the periplasm through a transmembrane protein RodZ (Domínguez‐Escobar et al, ; Garner et al, ; Morgenstein, Nguyen, & Gitai, ; van Teeffelen et al, ). MreB forms Rod complex with PG‐synthesizing enzymes, such as penicillin‐binding proteins (PBPs) (Blaauwen et al, ; Zhao, Patel, Helmann, & Dörr, ). Because MreB is a scaffold protein for the Rod complex, deletion of mreB gene or treatment of wild‐type (WT) cells with A22, which inhibits assembly of MreB, results in change of cell shape from rod to round (Bean et al, ; Doi et al, ; Iwai, Nagai, & Wachi, ; van den Ent et al, ).…”

Section: Introductionmentioning

confidence: 99%

Relation between rotation of MreB actin and cell width of Escherichia coli

et al. 2019

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Bacterial cells, including Escherichia coli and Bacillus subtilis, continuously elongate and divide. Although the cell width is maintained during cell cycle, the molecular mechanisms involved in its regulation remain unknown. MreB has been implicated to play a role in maintaining cell width. Several point mutations in mreB that affect cell width have been identified. The MreB protein forms clusters or polymers in the cell and moves along annular tracks perpendicular to the long axis. This rotation is coupled with peptidoglycan synthesis. Here, we focused on two MreB mutants, MreBA125V and MreBA174T. Cells producing MreBA125V and MreBA174T were thinner and thicker than WT cells, and MreBA125V and MreBA174T rotated faster and slower than WT MreB, respectively. We observed that the rotation rate correlated with the cell wall synthesis rate. Thus, we conclude that the velocity of MreB rotation also affects cell width, that is, the faster the MreB rotates, the thinner the cell width is.

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“…In support of this idea, aPBP activity was increased ( Lai et al, 2017 ) upon over-expression of the DD-endopeptidase MepS, which cleaves peptide bonds ( Singh et al, 2012 ). Therefore, Rod complex and aPBPs might serve different functions despite catalyzing the same chemical reactions ( Zhao et al, 2017 ; Pazos et al, 2017 ). In agreement with this viewpoint, recent work in the gram-positive Bacillus subtilis showed that the two machineries have opposing actions on cell diameter and lead to either circumferentially organized or disordered cell-wall deposition ( Dion et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Cell-wall synthases contribute to bacterial cell-envelope integrity by actively repairing defects

Vigouroux

Cordier

Aristov

et al. 2019

Preprint

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Cell shape and cell-envelope integrity of bacteria are determined by the peptidoglycan 12 cell wall. In rod-shaped Escherichia coli, two conserved sets of machinery are essential for cell-wall 13 insertion in the cylindrical part of the cell, the Rod complex and the class-A penicillin-binding 14 proteins (aPBPs). While the Rod complex governs rod-like cell shape, aPBP function is less well 15 understood. aPBPs were previously hypothesized to either work in concert with the Rod complex 16 or to independently repair cell-wall defects. First, we demonstrate through modulation of enzyme 17 levels that class-A PBPs do not contribute to rod-like cell shape but are required for mechanical 18 stability, supporting their independent activity. By combining measurements of cell-wall stiffness, 19 cell-wall insertion, and PBP1b motion at the single-molecule level we then demonstrate that PBP1b, 20 the major class-A PBP, contributes to cell-wall integrity by localizing and inserting peptidoglycan in 21 direct response to local cell-wall defects. 22 23 adjacent glycan strands. To avoid the formation of large pores in the cell wall during growth, cell-wall 29 insertion and cell-wall cleavage must be tightly coordinated (Vollmer et al., 2008). 30 Cell-wall insertion involves two kinds of enzymatic reactions: transglycosylase (TGase) activity to 31 extend the glycan strands, and transpeptidase (TPase) activity to create cross-links between glycan 32 strands. During side-wall elongation these two activities are carried out by two sets of machinery 33 (Cho et al., 2016). First, the Rod complex comprises the Penicillin-Binding Protein PBP2, an essential 34 transpeptidase (TPase), and RodA, an essential transglycosylase (TGase) and member of the SEDS 35 (shape, elongation, division and sporulation) family of proteins (Meeske et al., 2016; Emami et al., 36 2017). Together with the MreB cytoskeleton these and other Rod-complex components persistently 37 rotate around the cell (Lee et al., 2014; Cho et al., 2016) and are responsible for rod-like cell shape. 38 Second, bi-functional and essential class-A PBPs (aPBP's) PBP1a and PBP1b carry out both TPase and 39 TGase activities. PBP1a and PBP1b are activated by the outer-membrane lipoprotein cofactors LpoA 40 1 of 34 and LpoB, respectively (Typas et al., 2010; Paradis-Bleau et al., 2010; Typas et al., 2012). Mutants 41 in either PBP1a-LpoA or PBP1b-LpoB are viable and don't show any strong phenotype during 42 regular growth, but mutants in components from both pairs are synthetically lethal (Yousif et al., 43 1985; Typas et al., 2010; Paradis-Bleau et al., 2010). aPBPs also interact with cell-wall cleaving lytic 44 transglycosylases and DD-endopeptidases (Banzhaf et al., 2019), consistent with the possibility that 45 they form multi-enzyme complexes responsible for both cell-wall expansion and insertion. 46 In the past, aPBPs have been suggested to work in close association with the MreB-based 47 Rod complex (Pazos et al., 2017), motivated by biochemical interactions...

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Don’t let sleeping dogmas lie: new views of peptidoglycan synthesis and its regulation

Cited by 90 publications

References 122 publications

Lytic transglycosylases RlpA and MltC assist in Vibrio cholerae daughter cell separation

Lytic transglycosylases RlpA and MltC assist in Vibrio cholerae daughter cell separation

Relation between rotation of MreB actin and cell width of Escherichia coli

Cell-wall synthases contribute to bacterial cell-envelope integrity by actively repairing defects

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