Mechanistic aspects of maltotriose-conjugate translocation to the Gram-negative bacteria cytoplasm
| Autor: | Jean-Marie Pagès, Dmitrijs Lubriks, Jelena Pajovic, Koldo Morante, Satya Prathyusha Bhamidimarri, Jiajun Wang, Robert A. Stavenger, Julia Vergalli, Mathias Winterhalter, Estelle Dumont, Edgars Suna, Matthieu Réfrégiers |
|---|---|
| Přispěvatelé: | Membranes et cibles thérapeutiques (MCT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), University of Belgrade [Belgrade], Jacobs University [Bremen], Institute for Cell and Molecular Biosciences, Newcastle University [Newcastle], Latvian Institute of Organic Synthesis [Riga, Lituania], GlaxoSmithKline, Glaxo Smith Kline, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA)-Aix Marseille Université (AMU), Latvian Institute of Organic Synthesis, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cytoplasm Cell Membrane Permeability Health Toxicology and Mutagenesis Oligosaccharides Plant Science chemistry.chemical_compound Maltose-binding protein Gene Knockout Techniques Drug Resistance Multiple Bacterial Perylene Research Articles Ecology biology Escherichia coli Proteins food and beverages [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics Biochemistry Periplasmic Binding Proteins Periplasm Receptors Virus Efflux Bacterial Outer Membrane Proteins Research Article Gram-negative bacteria 030106 microbiology Porins Biochemistry Genetics and Molecular Biology (miscellaneous) Regulon Maltose-Binding Proteins 03 medical and health sciences Polysaccharides Operon Maltotriose Escherichia coli Maltose fungi Membrane Transport Proteins Periplasmic space biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology 030104 developmental biology chemistry biology.protein bacteria Trisaccharides |
| Zdroj: | Life Science Alliance Life Science Alliance, 2018, 2 (1), pp.e201800242. ⟨10.26508/lsa.201800242⟩ Life Science Alliance, Life Science Alliance LLC, 2018, 2 (1), pp.e201800242. ⟨10.26508/lsa.201800242⟩ |
| ISSN: | 2575-1077 |
| DOI: | 10.26508/lsa.201800242⟩ |
| Popis: | A maltotriose-conjugate can deliver molecules into the cytoplasmic space of Gram-negative bacteria by parasitizing the maltose uptake pathway. Small molecule accumulation in Gram-negative bacteria is a key challenge to discover novel antibiotics, because of their two membranes and efflux pumps expelling toxic molecules. An approach to overcome this challenge is to hijack uptake pathways so that bacterial transporters shuttle the antibiotic to the cytoplasm. Here, we have characterized maltodextrin–fluorophore conjugates that can pass through both the outer and inner membranes mediated by components of the Escherichia coli maltose regulon. Single-channel electrophysiology recording demonstrated that the compounds permeate across the LamB channel leading to accumulation in the periplasm. We have also demonstrated that a maltotriose conjugate distributes into both the periplasm and cytoplasm. In the cytoplasm, the molecule activates the maltose regulon and triggers the expression of maltose binding protein in the periplasmic space indicating that the complete maltose entry pathway is induced. This maltotriose conjugate can (i) reach the periplasmic and cytoplasmic compartments to significant internal concentrations and (ii) auto-induce its own entry pathway via the activation of the maltose regulon, representing an interesting prototype to deliver molecules to the cytoplasm of Gram-negative bacteria. |
| Databáze: | OpenAIRE |
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