ArticleThe Journal of biological chemistry2015
Structural analysis of a specialized type III secretion system peptidoglycan-cleaving enzyme.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- The type VI secretion system of Acinetobacter: mechanisms, biology and therapeutic potential.Communications biology · 2026Review
- Morphogenetic penicillin-binding proteins control virulence-associated type III secretion systems inInfection and immunity · 2025Article
- Structural insights into peptidoglycan glycosidase EtgA binding to the inner rod protein EscI of the type III secretion system via a designed EscI-EtgA fusion protein.Protein science : a publication of the Protein Society · 2024Article
- Measure of Peptidoglycan Degradation Activity.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Exploring the inhibition of the soluble lytic transglycosylase Cj0843c of Campylobacter jejuni via targeting different sites with different scaffolds.Protein science : a publication of the Protein Society · 2023Article
- Virulence-associated type III secretion systems in Gram-negative bacteria.Microbiology (Reading, England) · 2023Review
- Enhanced protein translocation to mammalian cells by expression of EtgA transglycosylase in a synthetic injector E. coli strain.Microbial cell factories · 2022Article
- Modulation of the Enzymatic Activity of the Flagellar Lytic Transglycosylase SltF by Rod Components and the Scaffolding Protein FlgJ inJournal of bacteriology · 2021Article
- T3S injectisome needle complex structures in four distinct states reveal the basis of membrane coupling and assembly.Nature microbiology · 2019Article
- On the road to structure-based development of anti-virulence therapeutics targeting the type III secretion system injectisome.MedChemComm · 2019Review
- Interplay between Peptidoglycan Biology and Virulence in Gram-Negative Pathogens.Microbiology and molecular biology reviews : MMBR · 2018Review
- EssH Peptidoglycan Hydrolase Enables Staphylococcus aureus Type VII Secretion across the Bacterial Cell Wall Envelope.Journal of bacteriology · 2018Article
- Bacterial type III secretion systems: a complex device for the delivery of bacterial effector proteins into eukaryotic host cells.FEMS microbiology letters · 2018Review
- Article
- Peptidoglycan hydrolysis mediated by the amidase AmiC and its LytM activator NlpD is critical for cell separation and virulence in the phytopathogen Xanthomonas campestris.Molecular plant pathology · 2018Article
- Article
- Lytic transglycosylases: concinnity in concision of the bacterial cell wall.Critical reviews in biochemistry and molecular biology · 2017Review
- Assembly, structure, function and regulation of type III secretion systems.Nature reviews. Microbiology · 2017Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The Gram-negative bacterium enteropathogenic Escherichia coli uses a syringe-like type III secretion system (T3SS) to inject virulence or "effector" proteins into the cytoplasm of host intestinal epithelial cells. To assemble, the T3SS must traverse both bacterial membranes, as well as the peptidoglycan layer. Peptidoglycan is made of repeating N-acetylmuramic acid and N-acetylglucosamine disaccharides cross-linked by pentapeptides to form a tight mesh barrier. Assembly of many macromolecular machines requires a dedicated peptidoglycan lytic enzyme (PG-lytic enzyme) to locally clear peptidoglycan. Here we have solved the first structure of a T3SS-associated PG-lytic enzyme, EtgA from enteropathogenic E. coli. Unexpectedly, the active site of EtgA has features in common with both lytic transglycosylases and hen egg white lysozyme. Most notably, the β-hairpin region resembles that of lysozyme and contains an aspartate that aligns with lysozyme Asp-52 (a residue critical for catalysis), a conservation not observed in other previously characterized lytic transglycosylase families to which the conserved T3SS enzymes had been presumed to belong. Mutation of the EtgA catalytic glutamate, Glu-42, conserved across lytic transglycosylases and hen egg white lysozyme, and this differentiating aspartate diminishes type III secretion in vivo, supporting its essential role in clearing the peptidoglycan for T3SS assembly. Finally, we show that EtgA forms a 1:1 complex with the building block of the polymerized T3SS inner rod component, EscI, and that this interaction enhances PG-lytic activity of EtgA in vitro, collectively providing the necessary strict localization and regulation of the lytic activity to prevent overall cell lysis.
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