PXD006546 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Disassembly of Functional Membrane Microdomains Relapses Antibiotic Resistance in Staphylococcus aureus |
Description | Bacteria 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. |
HostingRepository | PRIDE |
AnnounceDate | 2019-01-08 |
AnnouncementXML | Submission_2019-01-08_05:08:17.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jens Vanselow |
SpeciesList | scientific name: Staphylococcus aureus; NCBI TaxID: 1280; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-05-19 05:38:47 | ID requested | |
⏵ 1 | 2019-01-08 05:08:19 | announced | |
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 affiliation | Rudolf Virchow Center for Experimental Biomedicine University of Wuerzburg, Josef-Schneider-Str. 2 97080 Wuerzburg Germany |
contact email | andreas.schlosser@uni-wuerzburg.de |
lab head | |
Jens Vanselow |
contact affiliation | University Wuerzburg |
contact email | jens.vanselow@uni-wuerzburg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD006546
- Label: PRIDE project
- Name: Disassembly of Functional Membrane Microdomains Relapses Antibiotic Resistance in Staphylococcus aureus