PXD001494

PXD001494 is an original dataset announced via ProteomeXchange.

Title	Label-free quantitative proteomics reveals synergistic mechanism of a new erythromycin derivative and oxacillin against methcillin-resistant S. aureus
Description	Methicillin-resistant Staphylococcus aureus (MRSA) remains a global health threat with an over 14% fatality rate, in case of invasive infection, in 2011. Multi-drug resistance is the main reason for the failure of therapy. Use of antimicrobial drug combinations with synergistic effect is increasingly seen as a critical strategy to combat multi-drug resistant pathogens such as MRSA. However, the mechanism of synergistic effect has yet been systematically studied. In this work, we investigated a new erythromycin derivative, SIPI-8294, which has been demonstrated to have synergistic effect with oxacillin against MRSA, unlike its parent compound erythromycin. To obtain insights into the mechanism for the synergistic effect, label-free quantitative proteomics was employed. Cultured MRSA was exposed to sub-inhibitory doses of oxacillin, SIPI-8294, erythromycin, and combinations of SIPI-8294/oxacillin and erythromycin/oxacillin to reveal the global proteome responses to drug treatment. Results showed that 200 proteins were differentially expressed in SIPI-8294/oxacillin-treated cells. Among these proteins, the expression levels of penicillin binding protein 2a and β-lactamase, two proteins mainly responsible for oxacillin resistance, were four times lower in the SIPI-8294/oxacillin treatment group than in the erythromycin/oxacillin treatment group. Quantitative real-time PCR analysis also revealed similar trends at the transcription level. These results suggest that the synergistic mechanism may be related to interference with the known oxacillin resistance mechanism. The data also provided some evidence that the combination of SIPI-8294 and oxacillin appears to impact oxidation-reduction homeostasis and cell wall biosynthesis.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:48:37.591.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liu Xiaofen
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: 1280;
ModificationList	monohydroxylated residue; iodoacetic acid derivatized residue
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2014-11-17 01:25:14	ID requested
1	2022-02-28 17:08:09	announced
⏵ 2	2023-11-14 08:48:38	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: Key words: synergistic effect, label-free quantitative proteomics, oxacillin， methicillin-resistant S. aureus, erythromycin derivative

Henry Lam
contact affiliation	Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science and Technology
contact email	kehlam@ust.hk
lab head
Liu Xiaofen
contact affiliation	Chemical engineering
contact email	keliuxf@ust.hk
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/2022/03/PXD001494

PRIDE project URI

• PRIDE
  1. PXD001494
     1. Label: PRIDE project
     2. Name: Label-free quantitative proteomics reveals synergistic mechanism of a new erythromycin derivative and oxacillin against methcillin-resistant S. aureus