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PXD006546

PXD006546 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDisassembly of Functional Membrane Microdomains Relapses Antibiotic Resistance in Staphylococcus aureus
DescriptionBacteria spatially confine cellular processes like protease secretion and signal transduction in membrane platforms termed functional membrane microdomains, which in certain organisational and functional features resemble the lipid rafts of eukaryotic cells. However, a rigorous understanding of their composition, assembly and biological significance is unknown. Here we use the human pathogen methicillin-resistant Staphylococcus aureus (MRSA) to show that the organization of these platforms requires a preferential interaction between unphosphorylated membrane saccharolipids and the scaffold protein flotillin. This interaction leads to their accumulation in specific membrane microdomains concomitantly to the attraction of membrane-associated multimeric complexes, for which flotillin promotes efficient oligomerization. One of these harbored proteins is the penicillin-binding protein PBP2a, responsible for penicillin resistance in MRSA. We took PBP2a as showcase to demonstrate that flotillin mutants are also defective in PBP2a oligomerization and activity. Thus, perturbation of microdomains assembly, using commercially available drugs, interferes with PBP2a oligomerization and causes a relapse of MRSA penicillin resistance in vitro and in vivo, resulting in MRSA infections susceptible to conventional penicillin treatments. Our study shows that bacterial cells organize sophisticated programs for cellular compartmentalization and unravels a novel strategy to develop antimicrobial therapies for multi-drug resistance pathogens.
HostingRepositoryPRIDE
AnnounceDate2019-01-08
AnnouncementXMLSubmission_2019-01-08_05:08:17.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJens Vanselow
SpeciesList scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-05-19 05:38:47ID requested
12019-01-08 05:08:19announced
Publication List
Garc, í, a-Fern, á, ndez E, Koch G, Wagner RM, Fekete A, Stengel ST, Schneider J, Mielich-S, ü, ss B, Geibel S, Markert SM, Stigloher C, Lopez D, Membrane Microdomain Disassembly Inhibits MRSA Antibiotic Resistance. Cell, 171(6):1354-1367.e20(2017) [pubmed]
Keyword List
submitter keyword: Staphylococcus aureus, membrane platforms, DRM, DSM, LC-MS/MS
Contact List
Andreas Schlosser
contact affiliationRudolf Virchow Center for Experimental Biomedicine University of Wuerzburg, Josef-Schneider-Str. 2 97080 Wuerzburg Germany
contact emailandreas.schlosser@uni-wuerzburg.de
lab head
Jens Vanselow
contact affiliationUniversity Wuerzburg
contact emailjens.vanselow@uni-wuerzburg.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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