Project description
Insight into bacterial cell wall biogenesis
Gram-negative bacteria are defined by an outer membrane that protects the cell and mediates interactions with the environment and the host. This membrane relies on specialised proteins and lipoproteins, which must be precisely folded by endogenous cellular machinery. While these processes are well understood in Escherichia coli, little is known about how they operate in other major bacterial groups. The ERC-funded BactOMPbuild project focuses on bacteria of the phylum Bacteroidota, which include abundant human gut commensals, important pathogens and environmentally widespread species. The research will uncover how Bacteroidota assemble their outer membrane and how they transport surface lipoproteins. The project will reveal fundamental and medically relevant principles of bacterial cell envelope biogenesis.
Objective
Gram-negative bacteria are distinguished by the presence of an outer membrane (OM) at the cell periphery. This membrane is the site at which the bacterium interacts with its environment (or host if a pathogen), and provides the first line of defence against antibiotics, mechanical stresses, and immunological attacks. These functions depend on the presence of proteins that either span the outer membrane (Outer Membrane Proteins, or OMPs) or are anchored to the membrane by a lipid tail (lipoproteins). Sophisticated machinery is required to target, insert, and fold these proteins. Although this machinery is well-characterised in Escherichia coli and related organisms, it remains unclear how OM proteins are assembled in other major Gram-negative phyla.
In this project we aim to elucidate novel features of OM protein biogenesis in bacteria of the phylum Bacteroidota (formerly Bacteroidetes). The Bacteriodota are key human commensals, but also include major anaerobic pathogens, and are environmentally abundant. The pathways for OM protein biogenesis in the Bacteroidota differ from the E. coli paradigm in at least two major ways that we will investigate.
First, we have discovered that the Bam complex that is responsible for inserting OMPs into the OM has a very different composition from the E. coli paradigm and includes novel extracellular subunits. We now seek to identify the function(s) of these additional subunits and elucidate their molecular mechanism.
Second, in contrast to E. coli, the cell surface of Bacteroidota bacteria is coated with abundant lipoproteins (surface lipoproteins, or SLPs) that must be exported across the OM by a currently unknown mechanism. We aim to identify and characterise this SLP transporter as well as the novel pathway that our work has shown is needed for delivering SLPs to the OM.
To carry out these tasks we will employ in vivo and in vitro protein biochemistry, bacterial genetics, and structural analysis by cryoEM.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2024-ADG
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OX1 2JD Oxford
United Kingdom
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