Project description
Bacterial envelope interactions impacting antibiotic resistance
Gram-negative bacteria are resilient pathogens, primarily due to their tripartite envelope, which consists of the inner membrane, peptidoglycan cell wall, and outer membrane. Recent studies highlighted a crucial interaction between PG and the BAM complex, which coordinates the insertion of outer membrane proteins (OMPs), a process essential for proper envelope assembly. The ERC-funded Shape-En-Resist project will study the interactions that influence bacterial physiology and antibiotic resistance. It focuses on the assembly of lipopolysaccharide (LPS), its relationship with envelope biogenesis, and how these affect bacterial responses to antibiotics. The project also investigates the spatially heterogeneous nature of envelope biogenesis as a source of phenotypic diversity. It will combine microscopy, genetic screening, proteomics, and functionality assays.
Objective
Gram-negative bacteria are notoriously resilient, dominating the list of pathogens requiring urgent medical attention. Fundamental to their remarkable antibiotic resistance is a tripartite envelope comprised of an inner-membrane (IM), peptidoglycan cell wall (PG) and an outer membrane (OM). While these layers were previously viewed as separate compartments, it is becoming apparent that they work together in order to maintain envelope integrity. However, little is known about the crosstalk between components and molecular mechanisms orchestrating envelope assembly and functionality.
Our latest work has identified a key interaction between the PG and the BAM complex which inserts new OM proteins (OMPs), revealing a mechanism coordinating PG and OMP biogenesis and directing them both to the cell center. We posit that coordination is a key principle of envelope assembly and multiple interactions among envelope constituents are waiting to be discovered. In Shape-En-Resist we will uncover novel physical and genetic interactions, identify coordination mechanisms and elucidate their impact on bacterial physiology and antibiotic resistance. To this end, we will focus on three aims: (i) Explore the assembly of lipopolysaccharide (LPS), an endotoxin covering the bacterial surface, and characterize its interplay with envelope biogenesis. (ii) Comprehensively map PG-OMPs interactions and study how they affect bacterial response to antibiotics. (iii) Uncover the outcomes of spatially heterogenous envelope biogenesis and whether this process is a source of phenotypic diversity. To address these questions, a multidisciplinary approach will be taken, combining cutting-edge microscopy, advanced genetic screens, proteomics and novel functionality assays. We expect this project to uncover the interaction network amongst envelope components, reveal how it impacts the physiology of both single cells and bacterial populations, and ultimately expose the secrets of bacterial resilience.
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 biochemistry biomolecules proteins proteomics
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences basic medicine physiology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-STG
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91904 Jerusalem
Israel
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