CoChat
Sign Up
Cited by 2Bacterial Genetics and BiotechnologyEscherichia coli research studiesBiochemical and Structural Characterization

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

A novel peptidoglycan deacetylase modulates daughter cell separation in E. coli

Open access
Hernández-Rocamora, Víctor M., Martorana, Alessandra M., Belloso, Aitana, Ballesteros, Daniel, Zaccaria, Marta, Perez, Amilcar J., Iorga, Bogdan I., Abia, David, Gray, Joe, Breukink, Eefjan, Xiao, Jie, Pazos, Manuel, Polissi, Alessandra, Vollmer, Waldemar·2025·PLOS Genetics
DOI 10.1371/journal.pgen.1011626PMC PMC12440217

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Peptidoglycan hydrolases facilitate bacterial cell wall growth by creating space for insertion of new material and allowing physical separation of daughter cells. In Escherichia coli , three peptidoglycan amidases, AmiA, AmiB and AmiC, cleave septal peptidoglycan during cell division. The LytM-domain proteins EnvC, NlpD and ActS activate these amidases either from inside the cell or the outer membrane: EnvC binds to the cytoplasmic membrane-anchored divisome components FtsEX, while NlpD and ActS are outer membrane-anchored lipoproteins. Here we report the identification of a novel periplasmic deacetylase called SddA that removes acetyl groups from denuded peptidoglycan glycan strands, the products of amidases. The sddA gene is co-expressed with the gene encoding EnvC, linking SddA function to amidase activation. Consistent with this link, the deletion of sddA alleviates phenotypes associated with lack of amidase activation, while overexpression of sddA alleviates phenotypes related to a defective Tol-Pal system and causes cell chaining due to reduced septum peptidoglycan cleavage. We present a model according to which SddA modulates the activation of the septum-splitting amidases during cell division.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pgen.1011626

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 90

  1. W Vollmer, 2008, Peptidoglycan structure and architecture, FEMS Microbiol Rev, 32, 149, 10.1111/j.1574-6976.2007.00094.x · DOI
  2. AJF Egan, 2020, Regulation of peptidoglycan synthesis and remodelling, Nat Rev Microbiol, 18, 446, 10.1038/s41579-020-0366-3 · DOI · Paper page
  3. A Typas, 2011, From the regulation of peptidoglycan synthesis to bacterial growth and morphology, Nat Rev Microbiol, 10, 123, 10.1038/nrmicro2677 · DOI
  4. AN Gray, 2015, Coordination of peptidoglycan synthesis and outer membrane constriction during Escherichia coli cell division, Elife, 4
  5. G Mamou, 2022, Peptidoglycan maturation controls outer membrane protein assembly, Nature, 606, 953, 10.1038/s41586-022-04834-7 · DOI
  6. AW Bisson-Filho, 2017, Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division, Science, 355, 739, 10.1126/science.aak9973 · DOI
  7. X Yang, 2017, GTPase activity-coupled treadmilling of the bacterial tubulin FtsZ organizes septal cell wall synthesis, Science, 355, 744, 10.1126/science.aak9995 · DOI
  8. JM Monteiro, 2018, Peptidoglycan synthesis drives an FtsZ-treadmilling-independent step of cytokinesis, Nature, 554, 528, 10.1038/nature25506 · DOI
  9. CR Mahone, 2020, Bacterial cell division at a glance, J Cell Sci, 133, 10.1242/jcs.237057 · DOI
  10. M Pazos, 2021, Regulation and function of class A Penicillin-binding proteins, Curr Opin Microbiol, 60, 80, 10.1016/j.mib.2021.01.008 · DOI
  11. M Pazos, 2018, Z-ring membrane anchors associate with cell wall synthases to initiate bacterial cell division, Nat Commun, 9, 5090, 10.1038/s41467-018-07559-2 · DOI
  12. M Pazos, 2020, SPOR Proteins Are Required for Functionality of Class A Penicillin-Binding Proteins in Escherichia coli, mBio, 11, 10.1128/mBio.02796-20 · DOI
  13. M Pazos, 2017, Robust peptidoglycan growth by dynamic and variable multi-protein complexes, Curr Opin Microbiol, 36, 55, 10.1016/j.mib.2017.01.006 · DOI
  14. C Heidrich, 2001, Involvement of N-acetylmuramyl-L-alanine amidases in cell separation and antibiotic-induced autolysis of Escherichia coli, Mol Microbiol, 41, 167, 10.1046/j.1365-2958.2001.02499.x · DOI
  15. R Priyadarshini, 2007, Role of peptidoglycan amidases in the development and morphology of the division septum in Escherichia coli, J Bacteriol, 189, 5334, 10.1128/JB.00415-07 · DOI
  16. T Uehara, 2009, LytM-domain factors are required for daughter cell separation and rapid ampicillin-induced lysis in Escherichia coli, J Bacteriol, 191, 5094, 10.1128/JB.00505-09 · DOI
  17. Y Chen, 2024, Structure and activity of the septal peptidoglycan hydrolysis machinery crucial for bacterial cell division, PLoS Biol, 22, 10.1371/journal.pbio.3002628 · DOI
  18. A Hao, 2024, Structural insights into the FtsEX-EnvC complex regulation on septal peptidoglycan hydrolysis in Vibrio cholerae, Structure, 32
  19. X Xu, 2023, Mechanistic insights into the regulation of cell wall hydrolysis by FtsEX and EnvC at the bacterial division site, Proc Natl Acad Sci U S A, 120
  20. J Cook, 2023, Activator-induced conformational changes regulate division-associated peptidoglycan amidases, Proc Natl Acad Sci U S A, 120, 10.1073/pnas.2302580120 · DOI
  21. CK Gurnani Serrano, 2021, ActS activates peptidoglycan amidases during outer membrane stress in Escherichia coli, Mol Microbiol, 116, 329, 10.1111/mmi.14712 · DOI
  22. EA Mueller, 2021, The active repertoire of Escherichia coli peptidoglycan amidases varies with physiochemical environment, Mol Microbiol, 116, 311, 10.1111/mmi.14711 · DOI
  23. M-J Tsang, 2017, NlpD links cell wall remodeling and outer membrane invagination during cytokinesis in Escherichia coli, PLoS Genet, 13
  24. G Boelter, 2022, The lipoprotein DolP affects cell separation in Escherichia coli, but not as an upstream regulator of NlpD, Microbiology (Reading), 168, 10.1099/mic.0.001197 · DOI
  25. J Szczepaniak, 2020, The multifarious roles of Tol-Pal in Gram-negative bacteria, FEMS Microbiol Rev, 44, 490, 10.1093/femsre/fuaa018 · DOI
  26. W Vollmer, 2008, Structural variation in the glycan strands of bacterial peptidoglycan, FEMS Microbiol Rev, 32, 287, 10.1111/j.1574-6976.2007.00088.x · DOI
  27. W Vollmer, 2000, The pgdA gene encodes for a peptidoglycan N-acetylglucosamine deacetylase in Streptococcus pneumoniae, J Biol Chem, 275, 20496, 10.1074/jbc.M910189199 · DOI
  28. W Vollmer, 2002, Peptidoglycan N-acetylglucosamine deacetylase, a putative virulence factor in Streptococcus pneumoniae, Infect Immun, 70, 7176, 10.1128/IAI.70.12.7176-7178.2002 · DOI
  29. IG Boneca, 2007, A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system, Proc Natl Acad Sci U S A, 104, 997, 10.1073/pnas.0609672104 · DOI
  30. N Fittipaldi, 2008, Significant contribution of the pgdA gene to the virulence of Streptococcus suis, Mol Microbiol, 70, 1120, 10.1111/j.1365-2958.2008.06463.x · DOI
  31. G Wang, 2010, Peptidoglycan deacetylation in Helicobacter pylori contributes to bacterial survival by mitigating host immune responses, Infect Immun, 78, 4660, 10.1128/IAI.00307-10 · DOI
  32. MM Shaik, 2011, The structure of Helicobacter pylori HP0310 reveals an atypical peptidoglycan deacetylase, PLoS One, 6, 10.1371/journal.pone.0019207 · DOI
  33. LK Sycuro, 2010, Peptidoglycan crosslinking relaxation promotes Helicobacter pylori’s helical shape and stomach colonization, Cell, 141, 822, 10.1016/j.cell.2010.03.046 · DOI
  34. LK Sycuro, 2012, Multiple peptidoglycan modification networks modulate Helicobacter pylori’s cell shape, motility, and colonization potential, PLoS Pathog, 8, 10.1371/journal.ppat.1002603 · DOI
  35. C Chaput, 2006, Role of AmiA in the morphological transition of Helicobacter pylori and in immune escape, PLoS Pathog, 2, 10.1371/journal.ppat.0020097 · DOI
  36. C Chaput, 2007, Characterization of Helicobacter pylori lytic transglycosylases Slt and MltD, J Bacteriol, 189, 422, 10.1128/JB.01270-06 · DOI
  37. AV Patel, 2021, PGFinder, a novel analysis pipeline for the consistent, reproducible, and high-resolution structural analysis of bacterial peptidoglycans, Elife, 10, 10.7554/eLife.70597 · DOI
  38. B Glauner, 1988, The composition of the murein of Escherichia coli, Journal of Biological Chemistry, 263, 10088, 10.1016/S0021-9258(19)81481-3 · DOI
  39. B Glauner, 1988, Separation and quantification of muropeptides with high-performance liquid chromatography, Anal Biochem, 172, 451, 10.1016/0003-2697(88)90468-X · DOI
  40. Y Itoh, 2008, Roles of pgaABCD genes in synthesis, modification, and export of the Escherichia coli biofilm adhesin poly-beta-1,6-N-acetyl-D-glucosamine, J Bacteriol, 190, 3670, 10.1128/JB.01920-07 · DOI
  41. X Wang, 2004, The pgaABCD locus of Escherichia coli promotes the synthesis of a polysaccharide adhesin required for biofilm formation, J Bacteriol, 186, 2724, 10.1128/JB.186.9.2724-2734.2004 · DOI
  42. K Mendler, 2019, AnnoTree: visualization and exploration of a functionally annotated microbial tree of life, Nucleic Acids Res, 47, 4442, 10.1093/nar/gkz246 · DOI
  43. A Ursinus, 1994, Purification and properties of a membrane-bound lytic transglycosylase from Escherichia coli, J Bacteriol, 176, 338, 10.1128/jb.176.2.338-343.1994 · DOI
  44. J Lommatzsch, 1997, Outer membrane localization of murein hydrolases: MltA, a third lipoprotein lytic transglycosylase in Escherichia coli, J Bacteriol, 179, 5465, 10.1128/jb.179.17.5465-5470.1997 · DOI
  45. A Yahashiri, 2015, Bacterial SPOR domains are recruited to septal peptidoglycan by binding to glycan strands that lack stem peptides, Proc Natl Acad Sci U S A, 112, 11347, 10.1073/pnas.1508536112 · DOI
  46. A Ursinus, 2004, Murein (peptidoglycan) binding property of the essential cell division protein FtsN from Escherichia coli, J Bacteriol, 186, 6728, 10.1128/JB.186.20.6728-6737.2004 · DOI
  47. A Yahashiri, 2017, The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division, J Bacteriol, 199, 10.1128/JB.00118-17 · DOI
  48. P Müller, 2007, The essential cell division protein FtsN interacts with the murein (peptidoglycan) synthase PBP1B in Escherichia coli, J Biol Chem, 282, 36394, 10.1074/jbc.M706390200 · DOI
  49. SJR Arends, 2010, Discovery and characterization of three new Escherichia coli septal ring proteins that contain a SPOR domain: DamX, DedD, and RlpA, J Bacteriol, 192, 242, 10.1128/JB.01244-09 · DOI
  50. NH Georgopapadakou, 1982, Mode of action of azthreonam, Antimicrob Agents Chemother, 21, 950, 10.1128/AAC.21.6.950 · DOI
  51. AA Yakhnina, 2020, The Tol-Pal system is required for peptidoglycan-cleaving enzymes to complete bacterial cell division, Proc Natl Acad Sci U S A, 117, 6777, 10.1073/pnas.1919267117 · DOI
  52. E Cascales, 2001, The TolQ-TolR proteins energize TolA and share homologies with the flagellar motor proteins MotA-MotB, Mol Microbiol, 42, 795, 10.1046/j.1365-2958.2001.02673.x · DOI
  53. T Uehara, 2010, Daughter cell separation is controlled by cytokinetic ring-activated cell wall hydrolysis, EMBO J, 29, 1412, 10.1038/emboj.2010.36 · DOI
  54. GM Kaus, 2020, Lysozyme Resistance in Clostridioides difficile Is Dependent on Two Peptidoglycan Deacetylases, J Bacteriol, 202
  55. GS Dobihal, 2022, The WalR-WalK Signaling Pathway Modulates the Activities of both CwlO and LytE through Control of the Peptidoglycan Deacetylase PdaC in Bacillus subtilis, J Bacteriol, 204, 10.1128/jb.00533-21 · DOI
  56. S Arnaouteli, 2015, Two Putative Polysaccharide Deacetylases Are Required for Osmotic Stability and Cell Shape Maintenance in Bacillus anthracis, J Biol Chem, 290, 13465, 10.1074/jbc.M115.640029 · DOI
  57. H Coullon, 2018, N-Deacetylases required for muramic-δ-lactam production are involved in Clostridium difficile sporulation, germination, and heat resistance, J Biol Chem, 293, 18040, 10.1074/jbc.RA118.004273 · DOI
  58. A Benachour, 2012, The lysozyme-induced peptidoglycan N-acetylglucosamine deacetylase PgdA (EF1843) is required for Enterococcus faecalis virulence, J Bacteriol, 194, 6066, 10.1128/JB.00981-12 · DOI
  59. M Huber, 2019, Translational coupling via termination-reinitiation in archaea and bacteria, Nat Commun, 10, 4006, 10.1038/s41467-019-11999-9 · DOI
  60. LC Corbin Goodman, 2022, FtsZ at mid-cell is essential in Escherichia coli until the late stage of constriction, Microbiology (Reading), 168, 10.1099/mic.0.001194 · DOI
  61. N Silber, 2021, Progression of the late-stage divisome is unaffected by the depletion of the cytoplasmic FtsZ pool, Commun Biol, 4, 270, 10.1038/s42003-021-01789-9 · DOI
  62. T Baba, 2006, Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection, Mol Syst Biol, 2, 10.1038/msb4100050 · DOI · Paper page
  63. KA Datsenko, 2000, One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products, Proc Natl Acad Sci U S A, 97, 6640, 10.1073/pnas.120163297 · DOI
  64. EM Seco, 2022, Efficient markerless integration of genes in the chromosome of probiotic E. coli Nissle 1917 by bacterial conjugation, Microb Biotechnol, 15, 1374, 10.1111/1751-7915.13967 · DOI
  65. M Reddy, 2007, Role of FtsEX in cell division of Escherichia coli: viability of ftsEX mutants is dependent on functional SufI or high osmotic strength, J Bacteriol, 189, 98, 10.1128/JB.01347-06 · DOI
  66. TJ Silhavy, 1984, Experiments with gene fusions: Cold Spring Harbor Laboratory
  67. A Pennartz, 2009, Substrate-induced inactivation of the Escherichia coli AmiD N-acetylmuramoyl-L-alanine amidase highlights a new strategy to inhibit this class of enzyme, Antimicrob Agents Chemother, 53, 2991, 10.1128/AAC.01520-07 · DOI
  68. KE Van Straaten, 2004, Purification, crystallization and preliminary X-ray analysis of the lytic transglycosylase MltA from Escherichia coli, Acta Crystallogr D Biol Crystallogr, 60, 758, 10.1107/S0907444904002574 · DOI
  69. U Bertsche, 2006, Interaction between two murein (peptidoglycan) synthases, PBP3 and PBP1B, in Escherichia coli, Mol Microbiol, 61, 675, 10.1111/j.1365-2958.2006.05280.x · DOI
  70. AJF Egan, 2014, Outer-membrane lipoprotein LpoB spans the periplasm to stimulate the peptidoglycan synthase PBP1B, Proc Natl Acad Sci U S A, 111, 8197, 10.1073/pnas.1400376111 · DOI
  71. E Breukink, 2003, Lipid II is an intrinsic component of the pore induced by nisin in bacterial membranes, J Biol Chem, 278, 19898, 10.1074/jbc.M301463200 · DOI
  72. U Bertsche, 2005, In vitro murein peptidoglycan synthesis by dimers of the bifunctional transglycosylase-transpeptidase PBP1B from Escherichia coli, J Biol Chem, 280, 38096, 10.1074/jbc.M508646200 · DOI
  73. J Biboy, 2013, In vitro peptidoglycan synthesis assay with lipid II substrate., 273, 10.1007/978-1-62703-245-2_17 · DOI
  74. KJ Cutler, 2022, Omnipose: a high-precision morphology-independent solution for bacterial cell segmentation, Nat Methods, 19, 1438, 10.1038/s41592-022-01639-4 · DOI
  75. N Morè, 2019, Peptidoglycan Remodeling Enables Escherichia coli To Survive Severe Outer Membrane Assembly Defect, mBio, 10, 10.1128/mBio.02729-18 · DOI
  76. Z Lyu, 2022, FtsN maintains active septal cell wall synthesis by forming a processive complex with the septum-specific peptidoglycan synthases in E. coli, Nat Commun, 13, 5751, 10.1038/s41467-022-33404-8 · DOI
  77. FC Neidhardt, 1974, Culture medium for enterobacteria, J Bacteriol, 119, 736, 10.1128/jb.119.3.736-747.1974 · DOI
  78. I Letunic, 2024, Interactive Tree of Life (iTOL) v6: recent updates to the phylogenetic tree display and annotation tool, Nucleic Acids Res, 52, 10.1093/nar/gkae268 · DOI
  79. R Evans, 2022, Protein complex prediction with AlphaFold-Multimer
  80. HM Berman, 2000, The Protein Data Bank, Nucleic Acids Res, 28, 235, 10.1093/nar/28.1.235 · DOI · Paper page
  81. JC Gordon, 2005, H++: a server for estimating pKas and adding missing hydrogens to macromolecules, Nucleic Acids Res, 33, 10.1093/nar/gki464 · DOI
  82. DA Case, 2023, AmberTools, J Chem Inf Model, 63, 6183, 10.1021/acs.jcim.3c01153 · DOI
  83. C Tian, 2020, ff19SB: Amino-Acid-Specific Protein Backbone Parameters Trained against Quantum Mechanics Energy Surfaces in Solution, J Chem Theory Comput, 16, 528, 10.1021/acs.jctc.9b00591 · DOI
  84. S Izadi, 2014, Building Water Models: A Different Approach, J Phys Chem Lett, 5, 3863, 10.1021/jz501780a · DOI
  85. CW Hopkins, 2015, Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning, J Chem Theory Comput, 11, 1864, 10.1021/ct5010406 · DOI
  86. MR Shirts, 2017, Lessons learned from comparing molecular dynamics engines on the SAMPL5 dataset, J Comput Aided Mol Des, 31, 147, 10.1007/s10822-016-9977-1 · DOI
  87. RJ Loncharich, 1992, Langevin dynamics of peptides: the frictional dependence of isomerization rates of N-acetylalanyl-N’-methylamide, Biopolymers, 32, 523, 10.1002/bip.360320508 · DOI
  88. J Åqvist, 2004, Molecular dynamics simulations of water and biomolecules with a Monte Carlo constant pressure algorithm, Chemical Physics Letters, 384, 288, 10.1016/j.cplett.2003.12.039 · DOI
  89. T Darden, 1993, Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems, The Journal of Chemical Physics, 98, 10089, 10.1063/1.464397 · DOI
  90. DR Roe, 2013, PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data, J Chem Theory Comput, 9, 3084, 10.1021/ct400341p · DOI

Metadata

Authors
Hernández-Rocamora, V. M., Martorana, A. M., Belloso, A., Ballesteros, D., Zaccaria, M., Perez, A. J., Iorga, B. I., Abia, D., Gray, J., Breukink, E., Xiao, J., Pazos, M., Polissi, A., & Vollmer, W.
Affiliations
  • University of Milan (IT)
  • Consejo Superior de Investigaciones Científicas (ES)
  • Johns Hopkins University (US)
  • Centre National de la Recherche Scientifique (FR)
  • Newcastle University (GB)
  • Utrecht University (NL)
  • The University of Queensland (AU)
Corresponding author
Vollmer, Waldemar
ORCID
Venue
PLOS Genetics
Publisher
Public Library of Science (PLoS)
Published
2025-09-05
Volume
21
Issue
9
Pages
e1011626
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1011626
PMC
PMC12440217
OpenAlex
W4414037568
Cited by
2
References
6
Citations by year
2026: 1 · 2025: 1
FWCI
1.17
Type
journal article
Language
en
Update notices
new_version (2025-09-16)
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • Agence Nationale de la Recherche (ANR-20-PAMR-0010)
  • Biotechnology and Biological Sciences Research Council (BB/W005557/1, BB/W013630/1)
  • National Institute of General Medical Sciences (F32GM150262, R35GM136436)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
Keywords
Escherichia coli cell division, daughter cell separation, Amia, AMIC, ACT, periplasmic enzymes, Tol-Pal system, divisome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review