Self-Enhanced Accumulation of FtsN at Division Sites and Roles for Other Proteins with a SPOR Domain (DamX, DedD, and RlpA) in
            <i>Escherichia coli</i>
            Cell Constriction

Gerding, Matthew A.; Liu, Bing; Bendezú, Felipe O.; Hale, Cynthia A.; Bernhardt, Thomas G.; Boer, Piet A. J. de

doi:10.1128/jb.00811-09

Cited by 198 publications

(516 citation statements)

References 62 publications

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“…This ordinarily means that old peptidoglycan is not degraded unless the divisome is functioning properly. Consistent with previous studies suggesting a role for FtsN in activation of the divisome and initiation of septation and separation of daughter cells (5,(26)(27)(28), our results suggest that recruitment of FtsN functions to ensure that cell wall degradation does not take place unless new cell wall is being incorporated at the emergent poles. Also consistent with a regulatory rather than, for instance, an essential enzymatic role, mutants that are missing FtsN can be suppressed by mutations in another component of the divisome, FtsA (29).…”

Section: Discussionsupporting

confidence: 81%

Rapid β-lactam-induced lysis requires successful assembly of the cell division machinery

Chung

Yao

Goehring³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

113

116

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␤-lactam antibiotics inhibit penicillin binding proteins (PBPs) involved in peptidoglycan synthesis. Although inhibition of peptidoglycan biosynthesis is generally thought to induce cell lysis, the pattern and mechanism of cell lysis can vary substantially. ␤-lactams that inhibit FtsI, the only division specific PBP, block cell division and result in growth as filaments. These filaments ultimately lyse through a poorly understood mechanism. Here we find that one such ␤-lactam, cephalexin, can, under certain conditions, lead instead to rapid lysis at nascent division sites through a process that requires the complete and ordered assembly of the divisome, the essential machinery involved in cell division. We propose that this assembly process (in which the localization of cell wall hydrolases depends on properly targeted FtsN, which in turn depends on the presence of FtsI) ensures that the biosynthetic machinery to form new septa is in place before the machinery to degrade septated daughter cells is enabled. ␤-lactams that target FtsI subvert this mechanism by inhibiting FtsI without perturbing the normal assembly of the cell division machinery and the consequent activation of cell wall hydrolases. One seemingly paradoxical implication of our results is that ␤-lactam therapy may be improved by promoting active cell division.amidase ͉ cell wall hydrolase ͉ ftsN ͉ penicillin-binding proteins ͉ peptidoglycan

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Section: Discussionsupporting

confidence: 81%

Rapid β-lactam-induced lysis requires successful assembly of the cell division machinery

Chung

Yao

Goehring³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

113

116

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“…Septal localization of a Tat-targeted GFP-DamX SPOR fusion protein also was amidase dependent in vivo (Fig. S2), as previously reported (16).…”

Section: Spor Domains Bind Septal Regions Of Purifiedsupporting

confidence: 70%

“…4A). Because PaRlpA has a SPOR domain and localizes to division sites in vivo (16,17,27), it was necessary to verify that lack of GFPDamX SPOR binding did not result from competition for denuded glycans. We did so in two ways.…”

Section: Binding Of Spor Domains To Sacculi After Treatment With Pgmentioning

confidence: 99%

“…The length requirement suggests binding is cooperative or involves the formation of a higher-order structure of the SPOR domain with PG. In vivo, septal localization of all four E. coli SPOR domains requires both septal PG synthesis and amidase activity (16). Finally, amino acid substitutions in the SPOR Significance Cell division in bacteria is mediated by a large collection of proteins that assemble into a contractile ring at the division site.…”

mentioning

confidence: 99%

“…Several years ago it became apparent that a widespread subset of bacterial cell-division proteins is targeted to the division site by a small PG-binding domain known as a "SPOR" domain (15)(16)(17)(18). E. coli has four SPOR domain proteins, all of which are involved in cell division: DamX, DedD, FtsN, and RlpA.…”

mentioning

confidence: 99%

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Bacterial SPOR domains are recruited to septal peptidoglycan by binding to glycan strands that lack stem peptides

Yahashiri

Jorgenson

Weiss

2015

Proc. Natl. Acad. Sci. U.S.A.

102

142

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Bacterial SPOR domains bind peptidoglycan (PG) and are thought to target proteins to the cell division site by binding to "denuded" glycan strands that lack stem peptides, but uncertainties remain, in part because septal-specific binding has yet to be studied in a purified system. Here we show that fusions of GFP to SPOR domains from the Escherichia coli cell-division proteins DamX, DedD, FtsN, and RlpA all localize to septal regions of purified PG sacculi obtained from E. coli and Bacillus subtilis. Treatment of sacculi with an amidase that removes stem peptides enhanced SPOR domain binding, whereas treatment with a lytic transglycosylase that removes denuded glycans reduced SPOR domain binding. These findings demonstrate unequivocally that SPOR domains localize by binding to septal PG, that the physiologically relevant binding site is indeed a denuded glycan, and that denuded glycans are enriched in septal PG rather than distributed uniformly around the sacculus. Accumulation of denuded glycans in the septal PG of both E. coli and B. subtilis, organisms separated by 1 billion years of evolution, suggests that sequential removal of stem peptides followed by degradation of the glycan backbone is an ancient feature of PG turnover during bacterial cell division. Linking SPOR domain localization to the abundance of a structure (denuded glycans) present only transiently during biogenesis of septal PG provides a mechanism for coordinating the function of SPOR domain proteins with the progress of cell division.A defining feature of bacteria is the peptidoglycan (PG) cell wall or "sacculus" that confers cell shape, protects the cell against lysis caused by turgor pressure, and is the ultimate target of many clinically relevant antibiotics, including β-lactams and vancomycin (1-4). The structure of PG is characterized by a network of glycan strands connected at regular intervals by oligopeptide cross-links (Fig. 1). The glycans are built from a repeating disaccharide of β-1,4-linked N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), from which branch the oligopeptides that mediate cross-linking. During cell division, a new PG wall is assembled between the incipient daughter cells (5, 6), and subsequent cell separation depends on the activity of a collection of PG hydrolases that cleave various bonds in the PG mesh (7).In the model Gram-negative bacterium Escherichia coli, daughter-cell separation is driven primarily by three cell-wall amidases (8-10). These enzymes cleave the amide bond that joins the lactyl group of the MurNAc to the α-amino group of the first amino acid (L-Ala) of the stem peptide, releasing as products free oligopeptides and "denuded" glycan strands (Fig. 1). Lytic transglycosylases (LTs) that cleave the MurNAc-GlcNAc glycosidic bond and endopeptidases that cleave stem peptides make minor but still significant contributions to daughter-cell separation (9, 11). In Bacillus subtilis, a model Gram-positive species, the enzymology of daughter-cell separation is not as well characterized. The...

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Inhibitors of Bacterial Cell Partitioning

2013

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Self-Enhanced Accumulation of FtsN at Division Sites and Roles for Other Proteins with a SPOR Domain (DamX, DedD, and RlpA) in Escherichia coli Cell Constriction

Cited by 198 publications

References 62 publications

Rapid β-lactam-induced lysis requires successful assembly of the cell division machinery

Rapid β-lactam-induced lysis requires successful assembly of the cell division machinery

Bacterial SPOR domains are recruited to septal peptidoglycan by binding to glycan strands that lack stem peptides

Inhibitors of Bacterial Cell Partitioning

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