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Project

Project type/Form of grant
Title [sv]
Demontering av membranmikrodomäner i Staphylococcus aureus för att tämja antibiotikaresistens hos MRSA
Title [en]
Dismantling lipid rafts in Staphylococcus aureus to inhibit MRSA antibiotic resistance
Abstract [en]
Methicillin-resistant Staphylococcus aureus (MRSA) infection is a major global healthcare problem since this pathogen is resistant to all beta-lactam antibiotics. The overall aim of this research program is to innovate an alternative to combat this deadly pathogen. The strategy chosen builds on preliminary data which associates active PBP2a, the protein which is responsible for the MRSA multidrug resistance phenotype, to functional membrane microdomains (FMM). The flotillin FloA acts as scaffold of these assembly platforms and thus, either mutations on FloA or the use of anti-cholesterol drugs (i.e. statins) interfere with PBP2a oligomerization thereby inhibiting MRSA multidrug resistance both in vitro and in vivo. We propose to study the molecular basis underlying PBP2a oligomerization and the implementation of the use of anti-FMM drugs to fight MRSA infections. We will combine enzymology and genetics with cutting-edge cryo-electron microscopy, protein modelling, lipidomics and epidemiology to determine the basis of PBP2a oligomerization and its relevance in the acquisition of MRSA phenotype. Overall, our research program will provide provide insights about how protein recruitment by FMM may work as a general mechanism to turn on cellular activities in bacteria. Additionally, this project describes a path for MRSA domestication using statins, thus allowing recycling conventional antibiotics currently discarded due to the emergence of multidrug resistances.
Principal InvestigatorCava, Felipe
Coordinating organisation
Umeå University
Funder
Period
2018-12-01 - 2023-12-31
National Category
Infectious MedicineMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
DiVA, id: project:1615Project, id: 2018-05882_VR