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Architecture of bacterial lipid rafts; inhibition of virulence and antibiotic resistance using raft-disassembling small molecules

Objective

Membranes of eukaryotic cells organize signal transduction proteins into microdomains or lipid rafts whose integrity is essential for numerous cellular processes. Lipid rafts has been considered a fundamental step to define the cellular complexity of eukaryotes, assuming that bacteria do not require such a sophisticated organization of their signaling networks. However, I have discovered that bacteria organize many signaling pathways in membrane microdomains similar to the eukaryotic lipid rafts. Perturbation of bacterial lipid rafts leads to a potent and simultaneous impairment of all raft-harbored signaling pathways. Consequently, the disassembly of lipid rafts in pathogens like Staphylococcus aureus generates a simultaneous inhibition of numerous infection-related processes that can be further explored to control bacterial infections. This unexpected sophistication in membrane organization is unprecedented in bacteria and hence, this proposal will explore the molecular basis of the assembly of bacterial lipid rafts and their role in the infection-related processes. These questions will be addressed in three main goals: First, I will elucidate the molecular components and the mechanism of assembly of bacterial lipid rafts using S. aureus as model organism. Second, I will dissect the molecular basis that links the functionality of the infection-related processes to the integrity of bacterial lipid rafts. Third, my collection of anti-raft small molecules that are able to disrupt lipid rafts will be tested as antimicrobial agents to prevent hospital-acquired infections, abrogate pre-existing infections and develop bacteria-free materials that can be used in clinical settings. I will use a number of molecular approaches in combination with cutting-edge techniques in flow cytometry, cell-imaging and transcriptomics to clarify the architecture and functionality of lipid rafts and demonstrate the feasibility of targeting lipid a new strategy for anti-microbial therapy.

Field of science

  • /natural sciences/biological sciences/microbiology/bacteriology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug resistance/antibiotic resistance

Call for proposal

ERC-2013-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Address
Calle Serrano 117
28006 Madrid
Spain
Activity type
Research Organisations
EU contribution
€ 1 103 694
Principal investigator
Daniel López Serrano (Dr.)
Administrative Contact
Guillermo Sanjuanbenito (Mr.)

Beneficiaries (2)

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Spain
EU contribution
€ 1 103 694
Address
Calle Serrano 117
28006 Madrid
Activity type
Research Organisations
Principal investigator
Daniel López Serrano (Dr.)
Administrative Contact
Guillermo Sanjuanbenito (Mr.)
JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Germany
EU contribution
€ 389 432
Address
Sanderring 2
97070 Wuerzburg
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Christian Gloggengießer (Mr.)