PXD047096

PXD047096 is an original dataset announced via ProteomeXchange.

Title	The staphylococcal type VII secretion system impacts daptomycin sensitivity through controlling bacterial cell surface integrity
Description	The human pathogen Staphylococcus aureus encodes a specialised type VII secretion system (T7SS), which plays an important role in bacterial virulence during infection. However, the functions the T7SS during infection and in bacterial physiology remain unclear. Here we demonstrate that S. aureus strains lacking the transporter EssC as well as the T7SS effectors, EsxC and EsxA were highly sensitive to the important last resort drug, daptomycin as well as other membrane-targeting antibiotics, including gramicidin and bithionol. To understand how T7SS mediates increased antibiotic sensitivity, we investigated the impact of T7SS on the staphylococcal cell envelope. Interestingly, T7SS mutants displayed decreased membrane fluidity with altered localisation of cell membrane proteins such as flotillin under normal growth conditions. LC/MS analysis showed different protein profiles in the mutant membrane preparations compared to the WT, suggesting that T7SS impacts membrane homeostasis. Scanning electron microscopy analysis demonstrated distinct cell surface morphologies for the T7SS mutants, with altered cell wall synthesis as well cell surface charge. In line with the increased negative surface charge, daptomycin binding was enhanced in the mutants, which demonstrated increased membrane permeability when treated with the drug. T7SS mutants were more sensitive to daptomycin during intracellular infection, and furthermore, in a murine skin infection model, esxC mutants survived less than the WT when treated with daptomycin. Thus, our data show that the T7SS impacts sensitivity of S. aureus to membrane-acting drugs such as daptomycin through modulation of cell membrane integrity, indicating its potential as a drug target
HostingRepository	PRIDE
AnnounceDate	2024-04-19
AnnouncementXML	Submission_2024-04-19_01:25:25.273.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD047096
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andrew Bottrill
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-20 05:18:17	ID requested
⏵ 1	2024-04-19 01:25:25	announced

10.6019/PXD047096;

submitter keyword: cell membrane integrity, daptomycin, Warwick_RTP,Type VII secretion system, intracellular infection, membrane fluidity

Meera Unnikrishnan
contact affiliation	Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom
contact email	m.unnikrishnan@warwick.ac.uk
lab head
Andrew Bottrill
contact affiliation	University of Warwick
contact email	a.r.bottrill@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/04/PXD047096

PRIDE project URI

• PRIDE
  1. PXD047096
     1. Label: PRIDE project
     2. Name: The staphylococcal type VII secretion system impacts daptomycin sensitivity through controlling bacterial cell surface integrity