Roles of the DedD Protein in
            <i>Escherichia coli</i>
            Cell Constriction

Liu, Bing; Hale, Cynthia A.; Persons, Logan; Phillips-Mason, Polly J.; Boer, Piet A. J. de

doi:10.1128/jb.00698-18

Cited by 21 publications

(26 citation statements)

References 110 publications

(229 reference statements)

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“…An NMR-based approach was required due to the predicted combination of both structured and intrinsically disordered regions in DedD ( 38 ). The 1 H- 15 N correlation spectrum of 15 N-labeled DedD (residues 28 to 220 with a single transmembrane region removed) displayed both disperse peaks and intense narrow peaks with a very low 1 H chemical shift dispersion, confirming the presence of structured and unstructured regions ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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SPOR Proteins Are Required for Functionality of Class A Penicillin-Binding Proteins in Escherichia coli

Pazos

Peters

Boes

et al. 2020

mBio

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Sporulation-related repeat (SPOR) domains are present in many bacterial cell envelope proteins and are known to bind peptidoglycan. Escherichia coli contains four SPOR proteins, DamX, DedD, FtsN, and RlpA, of which FtsN is essential for septal peptidoglycan synthesis. DamX and DedD may also play a role in cell division, based on mild cell division defects observed in strains lacking these SPOR domain proteins. Here, we show by nuclear magnetic resonance (NMR) spectroscopy that the periplasmic part of DedD consists of a disordered region followed by a canonical SPOR domain with a structure similar to that of the SPOR domains of FtsN, DamX, and RlpA. The absence of DamX or DedD decreases the functionality of the bifunctional transglycosylase-transpeptidase penicillin-binding protein 1B (PBP1B). DamX and DedD interact with PBP1B and stimulate its glycosyltransferase activity, and DamX also stimulates the transpeptidase activity. DedD also binds to PBP1A and stimulates its glycosyltransferase activity. Our data support a direct role of DamX and DedD in enhancing the activity of PBP1B and PBP1A, presumably during the synthesis of the cell division septum. IMPORTANCE Escherichia coli has four SPOR proteins that bind peptidoglycan, of which FtsN is essential for cell division. DamX and DedD are suggested to have semiredundant functions in cell division based on genetic evidence. Here, we solved the structure of the SPOR domain of DedD, and we show that both DamX and DedD interact with and stimulate the synthetic activity of the peptidoglycan synthases PBP1A and PBP1B, suggesting that these class A PBP enzymes act in concert with peptidoglycan-binding proteins during cell division.

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Section: Resultsmentioning

confidence: 99%

“…DedD becomes essential in cells containing an FtsN version lacking the SPOR domain (FtsN slm117 ), a partially functional allele that supports cell viability ( 30 ). The SPOR domain of DedD is dispensable, but its transmembrane region and the adjacent periplasmic residues appear to be important for its function ( 38 ).…”

Section: Introductionmentioning

confidence: 99%

SPOR Proteins Are Required for Functionality of Class A Penicillin-Binding Proteins in Escherichia coli

Pazos

Peters

Boes

et al. 2020

mBio

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“…It is likely that uncoupling the FtsEX-mediated cell separation system from the septal PG synthesis machinery delays septal PG hydrolysis, leading to cell chaining. A delay in the production of denuded PG strands by the amidases would reduce the accumulation at the septum of SPOR domain proteins (including FtsN and DedD) that bind the denuded glycan strands (33,34). Decreased accumulation of these proteins would decrease the activation of FtsWI, leading to a decreased rate of septal PG synthesis and increased cell length.…”

Section: Discussionmentioning

confidence: 99%

Roles of ATP Hydrolysis by FtsEX and Interaction with FtsA in Regulation of Septal Peptidoglycan Synthesis and Hydrolysis

Pichoff

Lutkenhaus

2020

mBio

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ABSTRACT In Escherichia coli, FtsEX coordinates peptidoglycan (PG) synthesis and hydrolysis at the septum. It acts on FtsA in the cytoplasm to promote recruitment of septal PG synthetases and recruits EnvC, an activator of septal PG hydrolases, in the periplasm. Following recruitment, ATP hydrolysis by FtsEX is thought to regulate both PG synthesis and hydrolysis, but how it does this is not well understood. Here, we show that an ATPase mutant of FtsEX blocks septal PG synthesis similarly to cephalexin, suggesting that ATP hydrolysis by FtsEX is required throughout septation. Using mutants that uncouple the roles of FtsEX in septal PG synthesis and hydrolysis, we find that recruitment of EnvC to the septum by FtsEX, but not ATP hydrolysis, is required to promote cell separation when the NlpD-mediated cell separation system is present. However, ATP hydrolysis by FtsEX becomes necessary for efficient cell separation when the NlpD system is inactivated, suggesting that the ATPase activity of FtsEX is required for optimal activity of EnvC. Importantly, under conditions that suppress the role of FtsEX in cell division, disruption of the FtsEX-FtsA interaction delays cell separation, highlighting the importance of this interaction in coupling the cell separation system with the septal PG synthetic complex. IMPORTANCE Cytokinesis in Gram-negative bacteria requires coordinated invagination of the three layers of the cell envelope; otherwise, cells become sensitive to hydrophobic antibiotics and can even undergo cell lysis. In E. coli, the ABC transporter FtsEX couples the synthesis and hydrolysis of the stress-bearing peptidoglycan layer at the septum by interacting with FtsA and EnvC, respectively. ATP hydrolysis by FtsEX is critical for its function, but the reason why is not clear. Here, we find that in the absence of ATP hydrolysis, FtsEX blocks septal PG synthesis similarly to cephalexin. However, an FtsEX ATPase mutant, under conditions where it cannot block division, rescues ftsEX phenotypes as long as a partially redundant cell separation system is present. Furthermore, we find that the FtsEX-FtsA interaction is important for efficient cell separation.

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“…(i) Condition-dependent modulatory proteins in E. coli. Significant genetic data from many groups indicate that division proteins FtsEX, ZipA, FtsK, FtsN, FtsP, and DedD all share partially overlapping roles in stabilizing, and potentially activating, septal PG synthesis in E. coli (75)(76)(77)(78)(79)(80). While many of these proteins promote efficient division across culture conditions, several are strictly required for viability only during growth in particular environmental conditions.…”

Section: Responses To Environmental Threatsmentioning

confidence: 99%

Bacterial Cell Wall Quality Control during Environmental Stress

Mueller

Levin

2020

mBio

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Single-celled organisms must adapt their physiology to persist and propagate across a wide range of environmental conditions. The growth and division of bacterial cells depend on continuous synthesis of an essential extracellular barrier: the peptidoglycan cell wall, a polysaccharide matrix that counteracts turgor pressure and confers cell shape. Unlike many other essential processes and structures within the bacterial cell, the peptidoglycan cell wall and its synthesis machinery reside at the cell surface and are thus uniquely vulnerable to the physicochemical environment and exogenous threats. In addition to the diversity of stressors endangering cell wall integrity, defects in peptidoglycan metabolism require rapid repair in order to prevent osmotic lysis, which can occur within minutes. Here, we review recent work that illuminates mechanisms that ensure robust peptidoglycan metabolism in response to persistent and acute environmental stress. Advances in our understanding of bacterial cell wall quality control promise to inform the development and use of antimicrobial agents that target the synthesis and remodeling of this essential macromolecule. IMPORTANCE Nearly all bacteria are encased in a peptidoglycan cell wall, an essential polysaccharide structure that protects the cell from osmotic rupture and reinforces cell shape. The integrity of this protective barrier must be maintained across the diversity of environmental conditions wherein bacteria replicate. However, at the cell surface, the cell wall and its synthesis machinery face unique challenges that threaten their integrity. Directly exposed to the extracellular environment, the peptidoglycan synthesis machinery encounters dynamic and extreme physicochemical conditions, which may impair enzymatic activity and critical protein-protein interactions. Biotic and abiotic stressors—including host defenses, cell wall active antibiotics, and predatory bacteria and phage—also jeopardize peptidoglycan integrity by introducing lesions, which must be rapidly repaired to prevent cell lysis. Here, we review recently discovered mechanisms that promote robust peptidoglycan synthesis during environmental and acute stress and highlight the opportunities and challenges for the development of cell wall active therapeutics.

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Roles of the DedD Protein in Escherichia coli Cell Constriction

Cited by 21 publications

References 110 publications

SPOR Proteins Are Required for Functionality of Class A Penicillin-Binding Proteins in Escherichia coli

SPOR Proteins Are Required for Functionality of Class A Penicillin-Binding Proteins in Escherichia coli

Roles of ATP Hydrolysis by FtsEX and Interaction with FtsA in Regulation of Septal Peptidoglycan Synthesis and Hydrolysis

Bacterial Cell Wall Quality Control during Environmental Stress

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